An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
A characteristic symptom complex.
Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.
Changes in the organism associated with senescence, occurring at an accelerated rate.
A potent mutagen and carcinogen. This compound and its metabolite 4-HYDROXYAMINOQUINOLINE-1-OXIDE bind to nucleic acids. It inactivates bacteria but not bacteriophage.
An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.
An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.
An autosomal recessive syndrome occurring principally in females, characterized by the presence of reticulated, atrophic, hyperpigmented, telangiectatic cutaneous plaques, often accompanied by juvenile cataracts, saddle nose, congenital bone defects, disturbances in the growth of HAIR; NAILS; and TEETH; and HYPOGONADISM.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
The process by which a DNA molecule is duplicated.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Immunologically detectable substances found in the CELL NUCLEUS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs. (1/250)

The Saccharomyces cerevisiae Sgs1p helicase localizes to the nucleolus and is required to maintain the integrity of the rDNA repeats. Sgs1p is a member of the RecQ DNA helicase family, which also includes Schizo-saccharomyces pombe Rqh1, and the human BLM and WRN genes. These genes encode proteins which are essential to maintenance of genomic integrity and which share a highly conserved helicase domain. Here we show that recombinant Sgs1p helicase efficiently unwinds guanine-guanine (G-G) paired DNA. Unwinding of G-G paired DNA is ATP- and Mg2+-dependent and requires a short 3' single-stranded tail. Strikingly, Sgs1p unwinds G-G paired substrates more efficiently than duplex DNAs, as measured either in direct assays or by competition experiments. Sgs1p efficiently unwinds G-G paired telomeric sequences, suggesting that one function of Sgs1p may be to prevent telomere-telomere interactions which can lead to chromosome non-disjunction. The rDNA is G-rich and has considerable potential for G-G pairing. Diminished ability to unwind G-G paired regions may also explain the deleterious effect of mutation of Sgs1 on rDNA stability, and the accelerated aging characteristic of yeast strains that lack Sgs1 as well as humans deficient in the related WRN helicase.  (+info)

Human werner syndrome DNA helicase unwinds tetrahelical structures of the fragile X syndrome repeat sequence d(CGG)n. (2/250)

Formation of hairpin and tetrahelical structures by a d(CGG) trinucleotide repeat sequence is thought to cause expansion of this sequence and to engender fragile X syndrome. Here we show that human Werner syndrome DNA helicase (WRN), a member of the RecQ family of helicases, efficiently unwinds G'2 bimolecular tetraplex structures of d(CGG)7. Unwinding of d(CGG)7 by WRN requires hydrolyzable ATP and Mg2+ and is proportional to the amount of added helicase and to the time of incubation. The efficiencies of unwinding of G'2 d(CGG)7 tetraplex with 7 nucleotide-long single-stranded tails at their 3' or 5' ends are, respectively, 3.5- and 2-fold greater than that of double-stranded DNA. By contrast, WRN is unable to unwind a blunt-ended d(CGG)7 tetraplex, bimolecular tetraplex structures of a telomeric sequence 5'-d(TAGACATG(TTAGGG)2TTA)-3', or tetramolecular quadruplex forms of an IgG switch region sequence 5'-d(TACAGGGGAGCTGGGGTAGA)-3'. The ability of WRN to selectively unwind specific tetrahelices may reflect a specific role of this helicase in DNA metabolism.  (+info)

Werner syndrome helicase contains a 5'-->3' exonuclease activity that digests DNA and RNA strands in DNA/DNA and RNA/DNA duplexes dependent on unwinding. (3/250)

We show that WRN helicase contains a unique 5'-->3' exonuclease activity in the N-terminal region. Adeletion mutant lacking 231 N-terminal amino acid residues, made in a baculovirus system, did nothave this activity, while it showed ATPase and DNA helicase activities. This exonuclease activity was co-precipitated with the helicase activity using monoclonal antibodies specific to WRN helicase, indicating that it is an integral component with WRN helicase. The exonuclease in WRN helicase does not digest free single-stranded DNA or RNA, but it digests a strand in the duplex DNA or an RNA strand in a RNA/DNA heteroduplex in a 5'-->3' direction dependent on duplex unwinding. The digestion products were identified as 5'-mononucleotides. Our data show that WRN helicase needs a single-stranded 3' overhang region for efficient binding and unwinding of duplex molecules, while blunt-ended or 5' overhang duplex molecules were hardly unwound. These findings suggest that the WRN helicase and integral 5'-->3' exonuclease activities are involved in preventing a hyper-recombination by resolving entangled structures of DNA and RNA/DNA heteroduplexes that may be generated during rep-lication, repair and/or transcription.  (+info)

p53-mediated apoptosis is attenuated in Werner syndrome cells. (4/250)

The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53- mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients.  (+info)

The Werner syndrome protein is involved in RNA polymerase II transcription. (5/250)

Werner syndrome (WS) is a human progeroid syndrome characterized by the early onset of a large number of clinical features associated with the normal aging process. The complex molecular and cellular phenotypes of WS involve characteristic features of genomic instability and accelerated replicative senescence. The gene involved (WRN) was recently cloned, and its gene product (WRNp) was biochemically characterized as a helicase. Helicases play important roles in a variety of DNA transactions, including DNA replication, transcription, repair, and recombination. We have assessed the role of the WRN gene in transcription by analyzing the efficiency of basal transcription in WS lymphoblastoid cell lines that carry homozygous WRN mutations. Transcription was measured in permeabilized cells by [3H]UTP incorporation and in vitro by using a plasmid template containing the RNA polymerase II (RNA pol II)-dependent adenovirus major late promoter. With both of these approaches, we find that the transcription efficiency in different WS cell lines is reduced to 40-60% of the transcription in cells from normal individuals. This defect can be complemented by the addition of normal cell extracts to the chromatin of WS cells. Addition of purified wild-type WRNp but not mutated WRNp to the in vitro transcription assay markedly stimulates RNA pol II-dependent transcription carried out by nuclear extracts. A nonhelicase domain (a direct repeat of 27 amino acids) also appears to have a role in transcription enhancement, as revealed by a yeast hybrid-protein reporter assay. This is further supported by the lack of stimulation of transcription when mutant WRNp lacking this domain was added to the in vitro assay. We have thus used several approaches to show a role for WRNp in RNA pol II transcription, possibly as a transcriptional activator. A deficit in either global or regional transcription in WS cells may be a primary molecular defect responsible for the WS clinical phenotype.  (+info)

Physical and functional interaction between p53 and the Werner's syndrome protein. (6/250)

Werner's syndrome is a human autosomal recessive disorder leading to premature aging. The mutations responsible for this disorder have recently been localized to a gene (WRN) encoding a protein that possesses DNA helicase and exonuclease activities. Patients carrying WRN gene mutations exhibit an elevated rate of cancer, accompanied by increased genomic instability. The latter features are also characteristic of the loss of function of p53, a tumor suppressor that is very frequently inactivated in human cancer. Moreover, changes in the activity of p53 have been implicated in the onset of cellular replicative senescence. We report here that the WRN protein can form a specific physical interaction with p53. This interaction involves the carboxyl-terminal part of WRN and the extreme carboxyl terminus of p53, a region that plays an important role in regulating the functional state of p53. A small fraction of WRN can be found in complex with endogenous p53 in nontransfected cells. Overexpression of WRN leads to augmented p53-dependent transcriptional activity and induction of p21(Waf1) protein expression. These findings support the existence of a cross-talk between WRN and p53, which may be important for maintaining genomic integrity and for preventing the accumulation of aberrations that can give rise to premature senescence and cancer.  (+info)

Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. (7/250)

While all known natural isolates of C. elegans contain multiple copies of the Tc1 transposon, which are active in the soma, Tc1 transposition is fully silenced in the germline of many strains. We mutagenized one such silenced strain and isolated mutants in which Tc1 had been activated in the germline ("mutators"). Interestingly, many other transposons of unrelated sequence had also become active. Most of these mutants are resistant to RNA interference (RNAi). We found one of the mutated genes, mut-7, to encode a protein with homology to RNaseD. This provides support for the notion that RNAi works by dsRNA-directed, enzymatic RNA degradation. We propose a model in which MUT-7, guided by transposon-derived dsRNA, represses transposition by degrading transposon-specific messengers, thus preventing transposase production and transposition.  (+info)

Requirement of yeast SGS1 and SRS2 genes for replication and transcription. (8/250)

The SGS1 gene of the yeast Saccharomyces cerevisiae encodes a DNA helicase with homology to the human Bloom's syndrome gene BLM and the Werner's syndrome gene WRN. The SRS2 gene of yeast also encodes a DNA helicase. Simultaneous deletion of SGS1 and SRS2 is lethal in yeast. Here, using a conditional mutation of SGS1, it is shown that DNA replication and RNA polymerase I transcription are drastically inhibited in the srs2Delta sgs1-ts strain at the restrictive temperature. Thus, SGS1 and SRS2 function in DNA replication and RNA polymerase I transcription. These functions may contribute to the various defects observed in Werner's and Bloom's syndromes.  (+info)

Werner Syndrome is a rare, autosomal recessive genetic disorder characterized by the appearance of premature aging. It's often referred to as "progeria of the adult" or "adult progeria." The syndrome is caused by mutations in the WRN gene, which provides instructions for making a protein involved in repairing damaged DNA and maintaining the stability of the genetic information.

The symptoms typically begin in a person's late teens or early twenties and may include:
- Short stature
- Premature graying and loss of hair
- Skin changes, such as scleroderma (a thickening and hardening of the skin) and ulcers
- Voice changes
- Type 2 diabetes
- Cataracts
- Atherosclerosis (the buildup of fats, cholesterol, and other substances in and on the artery walls)
- Increased risk of cancer

The life expectancy of individuals with Werner Syndrome is typically around 45 to 50 years. It's important to note that while there are similarities between Werner Syndrome and other forms of progeria, such as Hutchinson-Gilford Progeria Syndrome, they are distinct conditions with different genetic causes and clinical features.

RecQ helicases are a group of enzymes that belong to the RecQ family, which are named after the E. coli RecQ protein. These helicases play crucial roles in maintaining genomic stability by participating in various DNA metabolic processes such as DNA replication, repair, recombination, and transcription. They are highly conserved across different species, including bacteria, yeast, plants, and mammals.

In humans, there are five RecQ helicases: RECQL1, RECQL4, RECQL5, BLM (RecQ-like helicase), and WRN (Werner syndrome ATP-dependent helicase). Defects in these proteins have been linked to various genetic disorders. For instance, mutations in the BLM gene cause Bloom's syndrome, while mutations in the WRN gene lead to Werner syndrome, both of which are characterized by genomic instability and increased cancer predisposition.

RecQ helicases possess 3'-5' DNA helicase activity, unwinding double-stranded DNA into single strands, and can also perform other functions like branch migration, strand annealing, and removal of protein-DNA crosslinks. Their roles in DNA metabolism help prevent and resolve DNA damage, maintain proper chromosome segregation during cell division, and ensure the integrity of the genome.

Exodeoxyribonucleases are a type of enzyme that cleave (break) nucleotides from the ends of DNA molecules. They are further classified into 5' exodeoxyribonucleases and 3' exodeoxyribonucleases based on the end of the DNA molecule they act upon.

5' Exodeoxyribonucleases remove nucleotides from the 5' end (phosphate group) of a DNA strand, while 3' exodeoxyribonucleases remove nucleotides from the 3' end (hydroxyl group) of a DNA strand.

These enzymes play important roles in various biological processes such as DNA replication, repair, and degradation. They are also used in molecular biology research for various applications such as DNA sequencing, cloning, and genetic engineering.

DNA helicases are a group of enzymes that are responsible for separating the two strands of DNA during processes such as replication and transcription. They do this by unwinding the double helix structure of DNA, using energy from ATP to break the hydrogen bonds between the base pairs. This allows other proteins to access the individual strands of DNA and carry out functions such as copying the genetic code or transcribing it into RNA.

During replication, DNA helicases help to create a replication fork, where the two strands of DNA are separated and new complementary strands are synthesized. In transcription, DNA helicases help to unwind the DNA double helix at the promoter region, allowing the RNA polymerase enzyme to bind and begin transcribing the DNA into RNA.

DNA helicases play a crucial role in maintaining the integrity of the genetic code and are essential for the normal functioning of cells. Defects in DNA helicases have been linked to various diseases, including cancer and neurological disorders.

A syndrome, in medical terms, is a set of symptoms that collectively indicate or characterize a disease, disorder, or underlying pathological process. It's essentially a collection of signs and/or symptoms that frequently occur together and can suggest a particular cause or condition, even though the exact physiological mechanisms might not be fully understood.

For example, Down syndrome is characterized by specific physical features, cognitive delays, and other developmental issues resulting from an extra copy of chromosome 21. Similarly, metabolic syndromes like diabetes mellitus type 2 involve a group of risk factors such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels that collectively increase the risk of heart disease, stroke, and diabetes.

It's important to note that a syndrome is not a specific diagnosis; rather, it's a pattern of symptoms that can help guide further diagnostic evaluation and management.

Exonucleases are a type of enzyme that cleaves nucleotides from the ends of a DNA or RNA molecule. They differ from endonucleases, which cut internal bonds within the nucleic acid chain. Exonucleases can be further classified based on whether they remove nucleotides from the 5' or 3' end of the molecule.

5' exonucleases remove nucleotides from the 5' end of the molecule, starting at the terminal phosphate group and working their way towards the interior of the molecule. This process releases nucleotide monophosphates (NMPs) as products.

3' exonucleases, on the other hand, remove nucleotides from the 3' end of the molecule, starting at the terminal hydroxyl group and working their way towards the interior of the molecule. This process releases nucleoside diphosphates (NDPs) as products.

Exonucleases play important roles in various biological processes, including DNA replication, repair, and degradation, as well as RNA processing and turnover. They are also used in molecular biology research for a variety of applications, such as DNA sequencing, cloning, and genome engineering.

Premature aging, also known as "accelerated aging" or "early aging," refers to the physiological process in which the body shows signs of aging at an earlier age than typically expected. This can include various symptoms such as wrinkles, graying hair, decreased energy and mobility, cognitive decline, and increased risk of chronic diseases.

The medical definition of premature aging is not well-established, as aging is a complex process influenced by a variety of genetic and environmental factors. However, certain conditions and syndromes are associated with premature aging, such as Hutchinson-Gilford progeria syndrome, Werner syndrome, and Down syndrome.

In general, the signs of premature aging may be caused by a combination of genetic predisposition, lifestyle factors (such as smoking, alcohol consumption, and poor diet), exposure to environmental toxins, and chronic stress. While some aspects of aging are inevitable, maintaining a healthy lifestyle and reducing exposure to harmful factors can help slow down the aging process and improve overall quality of life.

4-Nitroquinoline-1-oxide is a chemical compound that is often used in laboratory research as a carcinogenic agent. Its molecular formula is C6H4N2O3, and it is known to cause DNA damage and mutations, which can lead to the development of cancer. It is primarily used in scientific research to study the mechanisms of carcinogenesis and to test the effectiveness of potential cancer treatments.

It is important to note that 4-Nitroquinoline-1-oxide is not a medication or a treatment for any medical condition, and it should only be handled by trained professionals in a controlled laboratory setting.

Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), is a rare and fatal genetic condition characterized by the rapid aging of children. The term "progeria" comes from the Greek words "pro," meaning prematurely, and "gereas," meaning old age.

Individuals with progeria typically appear normal at birth but begin to display signs of accelerated aging within the first two years of life. These symptoms can include growth failure, loss of body fat and hair, aged-looking skin, joint stiffness, hip dislocation, and cardiovascular disease. The most common cause of death in progeria patients is heart attack or stroke due to widespread atherosclerosis (the hardening and narrowing of the arteries).

Progeria is caused by a mutation in the LMNA gene, which provides instructions for making a protein called lamin A. This protein is essential for the structure and function of the nuclear envelope, the membrane that surrounds the cell's nucleus. The mutation leads to the production of an abnormal form of lamin A called progerin, which accumulates in cells throughout the body, causing premature aging.

There is currently no cure for progeria, and treatment is focused on managing symptoms and complications. Researchers are actively studying potential treatments that could slow or reverse the effects of the disease.

Bloom syndrome is a rare genetic disorder characterized by short stature, sun-sensitive skin rash, and an increased risk of developing cancer. It is caused by mutations in the BLM gene, which provides instructions for making a protein that helps prevent tangles and knots from forming in DNA during cell division. As a result, cells with Bloom syndrome have a high rate of genetic recombination, leading to chromosomal instability and an increased risk of cancer.

Individuals with Bloom syndrome typically have a distinctive facial appearance, including a narrow face, small jaw, and a prominent nose. They may also have learning disabilities, fertility problems, and an increased susceptibility to infections. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the disorder. Bloom syndrome is typically diagnosed through genetic testing and chromosome analysis. Treatment is focused on managing the symptoms and reducing the risk of cancer through regular screenings and lifestyle modifications.

Rothmund-Thomson syndrome (RTS) is a rare genetic disorder characterized by the triad of poikiloderma, juvenile cataracts, and skeletal abnormalities. Poikiloderma is a skin condition that involves changes in coloration, including redness, brownish pigmentation, and telangiectasia (dilation of small blood vessels), as well as atrophy (wasting) of the skin.

The syndrome is caused by mutations in the RECQL4 gene, which plays a role in DNA repair. RTS has an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition.

Individuals with RTS may also experience other symptoms, such as sparse hair, short stature, small hands and feet, missing teeth, and a predisposition to developing certain types of cancer, particularly osteosarcoma (a type of bone cancer). The severity of the condition can vary widely among individuals.

RTS is typically diagnosed based on clinical features and genetic testing. Treatment is focused on managing the symptoms of the condition and may include measures such as sun protection to prevent skin damage, eye exams to monitor for cataracts, and regular cancer screenings.

A telomere is a region of repetitive DNA sequences found at the end of chromosomes, which protects the genetic data from damage and degradation during cell division. Telomeres naturally shorten as cells divide, and when they become too short, the cell can no longer divide and becomes senescent or dies. This natural process is associated with aging and various age-related diseases. The length of telomeres can also be influenced by various genetic and environmental factors, including stress, diet, and lifestyle.

DNA replication is the biological process by which DNA makes an identical copy of itself during cell division. It is a fundamental mechanism that allows genetic information to be passed down from one generation of cells to the next. During DNA replication, each strand of the double helix serves as a template for the synthesis of a new complementary strand. This results in the creation of two identical DNA molecules. The enzymes responsible for DNA replication include helicase, which unwinds the double helix, and polymerase, which adds nucleotides to the growing strands.

DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.

Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.

The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

Replication Protein A (RPA) is a single-stranded DNA binding protein complex that plays a crucial role in the process of DNA replication, repair, and recombination. In eukaryotic cells, RPA is composed of three subunits: RPA70, RPA32, and RPA14. The primary function of RPA is to coat single-stranded DNA (ssDNA) generated during these processes, protecting it from degradation, preventing the formation of secondary structures, and promoting the recruitment of other proteins involved in DNA metabolism.

RPA binds ssDNA with high affinity and specificity, forming a stable complex that protects the DNA from nucleases, chemical modifications, and other damaging agents. The protein also participates in the regulation of various enzymatic activities, such as helicase loading and activation, end processing, and polymerase processivity.

During DNA replication, RPA is essential for the initiation and elongation phases. It facilitates the assembly of the pre-replicative complex (pre-RC) at origins of replication, aids in the recruitment and activation of helicases, and promotes the switch from MCM2-7 helicase to polymerase processivity during DNA synthesis.

In addition to its role in DNA replication, RPA is involved in various DNA repair pathways, including nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). It also plays a critical role in meiotic recombination during sexual reproduction.

In summary, Replication Protein A (RPA) is a eukaryotic single-stranded DNA binding protein complex that protects, stabilizes, and regulates ssDNA during DNA replication, repair, and recombination processes.

Telomeric Repeat Binding Protein 2 (TRF2) is a protein that binds to the telomeres, which are the repetitive DNA sequences found at the ends of chromosomes. TRF2 plays a crucial role in protecting the telomeres from being recognized as damaged or broken DNA, which could otherwise lead to chromosomal instability and cellular senescence or apoptosis.

TRF2 is a member of the shelterin complex, a group of proteins that bind to and protect telomeres. TRF2 specifically binds to double-stranded TTAGGG repeats in the telomeric DNA through its N-terminal Myb-like DNA binding domain. By binding to the telomeres, TRF2 helps to prevent the activation of the DNA damage response (DDR) pathway and the subsequent activation of p53-dependent cell cycle checkpoints or apoptosis.

TRF2 has also been shown to play a role in regulating the length of telomeres. It can inhibit the activity of telomerase, an enzyme that adds repetitive DNA sequences to the ends of chromosomes, thereby limiting the extension of telomeres. TRF2 can also promote the formation of t-loops, a higher-order structure in which the 3' overhang of the telomere invades the double-stranded telomeric DNA, forming a displacement loop (D-loop). This helps to protect the telomere from being recognized as a double-strand break and degraded by nucleases.

Mutations in TRF2 have been associated with several human diseases, including premature aging disorders such as dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome, as well as cancer.

Adenosine triphosphatases (ATPases) are a group of enzymes that catalyze the conversion of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and inorganic phosphate. This reaction releases energy, which is used to drive various cellular processes such as muscle contraction, transport of ions across membranes, and synthesis of proteins and nucleic acids.

ATPases are classified into several types based on their structure, function, and mechanism of action. Some examples include:

1. P-type ATPases: These ATPases form a phosphorylated intermediate during the reaction cycle and are involved in the transport of ions across membranes, such as the sodium-potassium pump and calcium pumps.
2. F-type ATPases: These ATPases are found in mitochondria, chloroplasts, and bacteria, and are responsible for generating a proton gradient across the membrane, which is used to synthesize ATP.
3. V-type ATPases: These ATPases are found in vacuolar membranes and endomembranes, and are involved in acidification of intracellular compartments.
4. A-type ATPases: These ATPases are found in the plasma membrane and are involved in various functions such as cell signaling and ion transport.

Overall, ATPases play a crucial role in maintaining the energy balance of cells and regulating various physiological processes.

DNA repair is the process by which cells identify and correct damage to the DNA molecules that encode their genome. DNA can be damaged by a variety of internal and external factors, such as radiation, chemicals, and metabolic byproducts. If left unrepaired, this damage can lead to mutations, which may in turn lead to cancer and other diseases.

There are several different mechanisms for repairing DNA damage, including:

1. Base excision repair (BER): This process repairs damage to a single base in the DNA molecule. An enzyme called a glycosylase removes the damaged base, leaving a gap that is then filled in by other enzymes.
2. Nucleotide excision repair (NER): This process repairs more severe damage, such as bulky adducts or crosslinks between the two strands of the DNA molecule. An enzyme cuts out a section of the damaged DNA, and the gap is then filled in by other enzymes.
3. Mismatch repair (MMR): This process repairs errors that occur during DNA replication, such as mismatched bases or small insertions or deletions. Specialized enzymes recognize the error and remove a section of the newly synthesized strand, which is then replaced by new nucleotides.
4. Double-strand break repair (DSBR): This process repairs breaks in both strands of the DNA molecule. There are two main pathways for DSBR: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly rejoins the broken ends, while HR uses a template from a sister chromatid to repair the break.

Overall, DNA repair is a crucial process that helps maintain genome stability and prevent the development of diseases caused by genetic mutations.

Nuclear antigens are proteins or other molecules found in the nucleus of a cell that can stimulate an immune response and produce antibodies when they are recognized as foreign by the body's immune system. These antigens are normally located inside the cell and are not typically exposed to the immune system, but under certain circumstances, such as during cell death or damage, they may be released and become targets of the immune system.

Nuclear antigens can play a role in the development of some autoimmune diseases, such as systemic lupus erythematosus (SLE), where the body's immune system mistakenly attacks its own cells and tissues. In SLE, nuclear antigens such as double-stranded DNA and nucleoproteins are common targets of the abnormal immune response.

Testing for nuclear antigens is often used in the diagnosis and monitoring of autoimmune diseases. For example, a positive test for anti-double-stranded DNA antibodies is a specific indicator of SLE and can help confirm the diagnosis. However, it's important to note that not all people with SLE will have positive nuclear antigen tests, and other factors must also be considered in making a diagnosis.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Fibroblasts are specialized cells that play a critical role in the body's immune response and wound healing process. They are responsible for producing and maintaining the extracellular matrix (ECM), which is the non-cellular component present within all tissues and organs, providing structural support and biochemical signals for surrounding cells.

Fibroblasts produce various ECM proteins such as collagens, elastin, fibronectin, and laminins, forming a complex network of fibers that give tissues their strength and flexibility. They also help in the regulation of tissue homeostasis by controlling the turnover of ECM components through the process of remodeling.

In response to injury or infection, fibroblasts become activated and start to proliferate rapidly, migrating towards the site of damage. Here, they participate in the inflammatory response, releasing cytokines and chemokines that attract immune cells to the area. Additionally, they deposit new ECM components to help repair the damaged tissue and restore its functionality.

Dysregulation of fibroblast activity has been implicated in several pathological conditions, including fibrosis (excessive scarring), cancer (where they can contribute to tumor growth and progression), and autoimmune diseases (such as rheumatoid arthritis).

HeLa cells are a type of immortalized cell line used in scientific research. They are derived from a cancer that developed in the cervical tissue of Henrietta Lacks, an African-American woman, in 1951. After her death, cells taken from her tumor were found to be capable of continuous division and growth in a laboratory setting, making them an invaluable resource for medical research.

HeLa cells have been used in a wide range of scientific studies, including research on cancer, viruses, genetics, and drug development. They were the first human cell line to be successfully cloned and are able to grow rapidly in culture, doubling their population every 20-24 hours. This has made them an essential tool for many areas of biomedical research.

It is important to note that while HeLa cells have been instrumental in numerous scientific breakthroughs, the story of their origin raises ethical questions about informed consent and the use of human tissue in research.

Genomic instability is a term used in genetics and molecular biology to describe a state of increased susceptibility to genetic changes or mutations in the genome. It can be defined as a condition where the integrity and stability of the genome are compromised, leading to an increased rate of DNA alterations such as point mutations, insertions, deletions, and chromosomal rearrangements.

Genomic instability is a hallmark of cancer cells and can also be observed in various other diseases, including genetic disorders and aging. It can arise due to defects in the DNA repair mechanisms, telomere maintenance, epigenetic regulation, or chromosome segregation during cell division. These defects can result from inherited genetic mutations, acquired somatic mutations, exposure to environmental mutagens, or age-related degenerative changes.

Genomic instability is a significant factor in the development and progression of cancer as it promotes the accumulation of oncogenic mutations that contribute to tumor initiation, growth, and metastasis. Therefore, understanding the mechanisms underlying genomic instability is crucial for developing effective strategies for cancer prevention, diagnosis, and treatment.

Down syndrome is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is characterized by intellectual and developmental disabilities, distinctive facial features, and sometimes physical growth delays and health problems. The condition affects approximately one in every 700 babies born in the United States.

Individuals with Down syndrome have varying degrees of cognitive impairment, ranging from mild to moderate or severe. They may also have delayed development, including late walking and talking, and may require additional support and education services throughout their lives.

People with Down syndrome are at increased risk for certain health conditions, such as congenital heart defects, respiratory infections, hearing loss, vision problems, gastrointestinal issues, and thyroid disorders. However, many individuals with Down syndrome live healthy and fulfilling lives with appropriate medical care and support.

The condition is named after John Langdon Down, an English physician who first described the syndrome in 1866.

Cellular aging, also known as cellular senescence, is a natural process that occurs as cells divide and grow older. Over time, cells accumulate damage to their DNA, proteins, and lipids due to various factors such as genetic mutations, oxidative stress, and epigenetic changes. This damage can impair the cell's ability to function properly and can lead to changes associated with aging, such as decreased tissue repair and regeneration, increased inflammation, and increased risk of age-related diseases.

Cellular aging is characterized by several features, including:

1. Shortened telomeres: Telomeres are the protective caps on the ends of chromosomes that shorten each time a cell divides. When telomeres become too short, the cell can no longer divide and becomes senescent or dies.
2. Epigenetic changes: Epigenetic modifications refer to chemical changes to DNA and histone proteins that affect gene expression without changing the underlying genetic code. As cells age, they accumulate epigenetic changes that can alter gene expression and contribute to cellular aging.
3. Oxidative stress: Reactive oxygen species (ROS) are byproducts of cellular metabolism that can damage DNA, proteins, and lipids. Accumulated ROS over time can lead to oxidative stress, which is associated with cellular aging.
4. Inflammation: Senescent cells produce pro-inflammatory cytokines, chemokines, and matrix metalloproteinases that contribute to a low-grade inflammation known as inflammaging. This chronic inflammation can lead to tissue damage and increase the risk of age-related diseases.
5. Genomic instability: DNA damage accumulates with age, leading to genomic instability and an increased risk of mutations and cancer.

Understanding cellular aging is crucial for developing interventions that can delay or prevent age-related diseases and improve healthy lifespan.

Metabolic syndrome, also known as Syndrome X, is a cluster of conditions that increase the risk of heart disease, stroke, and diabetes. It is not a single disease but a group of risk factors that often co-occur. According to the American Heart Association and the National Heart, Lung, and Blood Institute, a person has metabolic syndrome if they have any three of the following five conditions:

1. Abdominal obesity (waist circumference of 40 inches or more in men, and 35 inches or more in women)
2. Triglyceride level of 150 milligrams per deciliter of blood (mg/dL) or greater
3. HDL cholesterol level of less than 40 mg/dL in men or less than 50 mg/dL in women
4. Systolic blood pressure of 130 millimeters of mercury (mmHg) or greater, or diastolic blood pressure of 85 mmHg or greater
5. Fasting glucose level of 100 mg/dL or greater

Metabolic syndrome is thought to be caused by a combination of genetic and lifestyle factors, such as physical inactivity and a diet high in refined carbohydrates and unhealthy fats. Treatment typically involves making lifestyle changes, such as eating a healthy diet, getting regular exercise, and losing weight if necessary. In some cases, medication may also be needed to manage individual components of the syndrome, such as high blood pressure or high cholesterol.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Single-stranded DNA (ssDNA) is a form of DNA that consists of a single polynucleotide chain. In contrast, double-stranded DNA (dsDNA) consists of two complementary polynucleotide chains that are held together by hydrogen bonds.

In the double-helix structure of dsDNA, each nucleotide base on one strand pairs with a specific base on the other strand through hydrogen bonding: adenine (A) with thymine (T), and guanine (G) with cytosine (C). This base pairing provides stability to the double-stranded structure.

Single-stranded DNA, on the other hand, lacks this complementary base pairing and is therefore less stable than dsDNA. However, ssDNA can still form secondary structures through intrastrand base pairing, such as hairpin loops or cruciform structures.

Single-stranded DNA is found in various biological contexts, including viral genomes, transcription bubbles during gene expression, and in certain types of genetic recombination. It also plays a critical role in some laboratory techniques, such as polymerase chain reaction (PCR) and DNA sequencing.

Human chromosome pair 8 consists of two rod-shaped structures present in the nucleus of each cell of the human body. Each chromosome is made up of DNA tightly coiled around histone proteins, forming a complex structure known as a chromatin.

Human cells have 23 pairs of chromosomes, for a total of 46 chromosomes. Pair 8 is one of the autosomal pairs, meaning that it is not a sex chromosome (X or Y). Each member of chromosome pair 8 has a similar size, shape, and banding pattern, and they are identical in males and females.

Chromosome pair 8 contains several genes that are essential for various cellular functions and human development. Some of the genes located on chromosome pair 8 include those involved in the regulation of metabolism, nerve function, immune response, and cell growth and division.

Abnormalities in chromosome pair 8 can lead to genetic disorders such as Wolf-Hirschhorn syndrome, which is caused by a partial deletion of the short arm of chromosome 4, or partial trisomy 8, which results from an extra copy of all or part of chromosome 8. Both of these conditions are associated with developmental delays, intellectual disability, and various physical abnormalities.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

... (WS) or Werner's syndrome, also known as "adult progeria", is a rare, autosomal recessive disorder which is ... Werner syndrome is named after the German scientist Otto Werner. He identified the syndrome in four siblings observed with ... Otto Werner was the first to observe Werner syndrome in 1904 as a part of his dissertation research. As a German ... Progeroid syndromes, Syndromes affecting stature, Syndromes affecting bones, Syndromes affecting the nervous system, Diseases ...
Werner syndrome is caused by mutations in the WRN gene. More than 20 mutations in the WRN gene are known to cause Werner ... Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by ... Werner syndrome ATP-dependent helicase has been shown to interact with: BLM DNA-PKcs, FEN1, Ku70, Ku80, P53, PCNA, TERF2, and ... Lebel M (2001). "Werner syndrome: genetic and molecular basis of a premature aging disorder". Cell. Mol. Life Sci. 58 (7): 857- ...
Werner syndrome, a condition associated with premature aging, causes a "bird-like" appearance due to pinching of the nose. Down ... eds.). Werner Syndrome. PMID 20301687. Archived from the original on 2017-01-18. Retrieved 2017-08-31 - via NCBI. {{cite book ... Empty nose syndrome, a nose crippled by excessive resection of the inferior and/or middle turbinates of the nose Dried nasal ... in Kallmann syndrome or Parkinson's disease. A blocked sinus ostium, an opening from a paranasal sinus, will cause fluid to ...
Some segmental progeroid syndromes, such as Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndromes (RTS) and ... Werner syndrome (WS) Bloom syndrome (BS) Rothmund-Thomson syndrome (RTS) Cockayne syndrome (CS) Xeroderma pigmentosum (XP) ... Examples of PS include Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), Cockayne syndrome (CS), ... Hutchinson-Gilford progeria syndrome, Werner syndrome, and Cockayne syndrome are the three genetic disorders in which patients ...
Rothmund-Thomson syndrome, Werner syndrome and Xeroderma pigmentosum. Although cancer syndromes exhibit an increased risk of ... A hereditary cancer syndrome (familial/family cancer syndrome, inherited cancer syndrome, cancer predisposition syndrome, ... Lynch syndrome), Howel-Evans syndrome of esophageal cancer with tylosis, juvenile polyposis syndrome, Li-Fraumeni syndrome, ... Birt-Hogg-Dubé syndrome, Carney syndrome, familial chordoma, Cowden syndrome, dysplastic nevus syndrome with familial melanoma ...
... and Werner syndrome. Horvath published the first article demonstrating that trisomy 21 (Down syndrome) is associated with ... Maierhofer, A (2017). "Accelerated epigenetic aging in Werner syndrome". Aging. 9 (4): 1143-1152. doi:10.18632/aging.101217. ... physical activity and the risks associated with metabolic syndrome. Horvath and Raj proposed an epigenetic clock theory of ... "Accelerated epigenetic aging in Down syndrome". Aging Cell. 14 (3): 491-5. doi:10.1111/acel.12325. PMC 4406678. PMID 25678027. ...
Maierhofer A, Flunkert J, Oshima J, Martin GM, Haaf T, Horvath S (April 2017). "Accelerated epigenetic aging in Werner syndrome ... Adult progeria also known as Werner syndrome is associated with epigenetic age acceleration in blood. Fibroblast samples from ... Down syndrome entails an increased risk of many chronic diseases that are typically associated with older age. The clinical ... Children with a very rare disorder known as syndrome X maintain the façade of persistent toddler-like features while aging from ...
"LMNA mutations in atypical Werner's syndrome". Lancet. 362 (9382): 440-5. doi:10.1016/S0140-6736(03)14069-X. PMID 12927431. ... Mutations in lamin A (LMNA) cause Hutchinson-Gilford progeria syndrome, a dramatic form of premature aging. Mouse cells ... 2004). "Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis". Nature ... Rusinal AE, Sinensky MS (2006). "Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors". J. Cell Sci. ...
... and Cockayne syndrome (mean lifespan 13 years). Werner syndrome is due to an inherited defect in an enzyme (a helicase and ... Werner syndrome (WS), a premature aging condition in humans, is caused by a genetic defect in a RecQ helicase that is employed ... Bloom syndrome and Rothmund-Thomson syndrome. In addition to human inherited syndromes, experimental mouse models with genetic ... Harrigan, JA; Wilson, DM; Prasad, R; Opresko, PL; Beck, G; May, A; Wilson, SH; Bohr, VA (Jan 2006). "The Werner syndrome ...
Martin's group separately identified the genetic defect causing the aging disease Werner syndrome, and its underlying ... September 1994). "Integrated mapping analysis of the Werner syndrome region of chromosome 8" (PDF). Genomics. 23 (1): 100-13. ... "The Werner syndrome protein is a DNA helicase". Nature Genetics. 17 (1): 100-103. doi:10.1038/ng0997-100. ISSN 1061-4036. PMID ... "The Werner syndrome protein is involved in RNA polymerase II transcription". Molecular Biology of the Cell. 10 (8): 2655-2668. ...
Hutchinson-Gilford progeria syndrome) Rothmund-Thomson syndrome Trichothiodystrophy Werner syndrome Xeroderma pigmentosum Some ... Rossi ML, Ghosh AK, Bohr VA (2010). "Roles of Werner syndrome protein in protection of genome integrity". DNA Repair (Amst.). 9 ... Bohr VA (2005). "Deficient DNA repair in the human progeroid disorder, Werner syndrome". Mutat. Res. 577 (1-2): 252-9. doi: ... Saintigny Y, Makienko K, Swanson C, Emond MJ, Monnat RJ (2002). "Homologous recombination resolution defect in werner syndrome ...
1996). "Positional cloning of the Werner's syndrome gene". Science. 272 (5259): 258-262. Bibcode:1996Sci...272..258Y. doi: ... Werner syndrome) and early onset Alzheimer's disease (presenilin 2). In 1997, Fu returned to academia, taking the position of ... While there, she was part of the team that identified the fragile-X syndrome gene. The gene contains a polymorphic CGG ... This mutational mechanism is now known to cause not only Fragile X syndrome and Myotonic dystrophy, but also Huntington's ...
NCBI: Human Gene Map eMedicine: Progeria (Werner Syndrome) Who Named It? C. W. Otto Werner Genetic Disorders: Werner Syndrome v ... after whom Werner syndrome, a form of progeria, was named. As a medical student in 1903, Werner observed the syndrome in four ... Werner was born in Flensburg, the son of a provincial councillor. He attended school in Kiel and qualified to practice medicine ... Carl Wilhelm Otto Werner (1 February 1879 - 5 June 1936) was a German physician, ...
... "p53 Modulates the exonuclease activity of Werner syndrome protein". The Journal of Biological Chemistry. 276 (37): 35093-102. ... Yu A, Fan HY, Liao D, Bailey AD, Weiner AM (May 2000). "Activation of p53 or loss of the Cockayne syndrome group B repair ... Abramovitch S, Werner H (2003). "Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of ... GeneReviews/NCBI/NIH/UW entry on Li-Fraumeni Syndrome TUMOR PROTEIN p53 @ OMIM p53 restoration of function p53 @ The Atlas of ...
MDPL/MDP, AWS and Werner's syndrome all present with progeria. A first example of germline transmission was observed in a ... POLD1 Ser605del and R507C variants have also been identified in a subset of patients with atypical Werner's syndrome (AWS). ... The WRN gene is mutated in Werner syndrome (an autosomal recessive disorder) leading to accelerated aging and increased genetic ... Kamath-Loeb AS, Shen JC, Schmitt MW, Loeb LA (April 2012). "The Werner syndrome exonuclease facilitates DNA degradation and ...
Werner syndrome, also known as "adult progeria", is another single-gene genetic disease. it is caused by a mutation in the wrn ... Those who have Werner syndrome are at an increased risk for cataracts, type 2 diabetes, different types of cancers, and ... S2CID 11798376 "Werner syndrome". Genetics Home Reference. Retrieved 2020-04-11. Yamamoto K, Imakiire A, Miyagawa N, Kasahara T ... There are four common traits of Werner's syndrome: cataracts in both eyes, changes in skin similar to scleroderma, short ...
Werner's syndrome is a genetic disorder that causes premature aging. Patients with Werner's syndrome lack a functional WRN ... Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD (September 2008). "The Werner syndrome protein binds replication fork ... such as cancer and Werner's Disease. The first theoretical description of cruciform-forming DNA structures was hypothesized in ...
Werner syndrome and pernicious anemia can also cause premature graying. A 2005 uncontrolled study demonstrated that people 50- ... Marie Antoinette syndrome is a proposed phenomenon in which sudden whitening is caused by stress. It has been found that some ... Waardenburg syndrome or a vitamin B12 deficiency. At some point in the human life cycle, cells that are located in the base of ...
Werner syndrome (WS) is a premature aging condition in humans. WS is caused by a genetic defect in a RecQ helicase that is ... Didangelos A, Simper D, Monaco C, Mayr M (May 2009). "Proteomics of acute coronary syndromes". Current Atherosclerosis Reports ...
WRN helicase, which is mutated in Werner Syndrome patients, is required for efficient replication of the telomeric G-strand. ... which is responsible for the heightened cancer incidence in individuals with Werner Syndrome. He went on to show that following ... Karlseder discovered that telomere dysfunction plays a role in Werner Syndrome, a premature aging disease that is associated ... "Telomere dysfunction as a cause of genomic instability in Werner syndrome". Proceedings of the National Academy of Sciences. ...
Werner syndrome is a condition in humans characterized by accelerated aging. It is caused by mutations in the gene WRN that ... November 2019). "Evidence for premature aging in a Drosophila model of Werner syndrome". Experimental Gerontology. 127: 110733 ...
... which causes Werner's Syndrome, the MAPT mutations which cause FTLD-tau type, and subsequently the MAPT association with Guam ... he was the senior author of a Science article locating the gene and mutations responsible for Werner syndrome, a form of ... "Integrated Mapping Analysis of the Werner Syndrome Region of Chromosome 8". Genomics. 23 (1): 100-113. doi:10.1006/geno. ... "Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: lessons learned from ...
"Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases". J. Biol. Chem. 277 (43): 41110- ... Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome. The Bloom ... and functional interaction between Werner and Bloom syndrome proteins". J. Biol. Chem. 277 (24): 22035-44. doi:10.1074/jbc. ... "Bloom syndrome". Genetics Home Reference. NIH. Retrieved 19 March 2013. De Muyt A, Jessop L, Kolar E, Sourirajan A, Chen J, ...
Researchers at INMEGEN also study Werner syndrome and the pulmonary adenocarcinoma. INMEGEN has many investigations related to ... Another study is on the effect of Omega 3 on metabolic syndrome in the Mexican population, specifically on early biomarkers ...
Werner's syndrome is a rare autosomal recessive disorder characterized by premature aging. The protein encoded by this gene ... WRNIP1 has been shown to interact with Werner syndrome ATP-dependent helicase. GRCh38: Ensembl release 89: ENSG00000124535 - ... "A novel protein interacts with the Werner's syndrome gene product physically and functionally". J Biol Chem. 276 (23): 20364-9 ... "Entrez Gene: WRNIP1 Werner helicase interacting protein 1". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to ...
Herlyn-Werner-Wunderlich syndrome is one such syndrome in which unilateral renal agenesis is combined with a blind hemivagina ... Ahmad, Zohra; Goyal, Ankur; Das, Chandan J; Deka, Dipika; Sharma, Raju (2013-01-01). "Herlyn-Werner-Wunderlich syndrome ... Kallmann syndrome, branchio-oto-renal syndrome and others.[citation needed] The prevalence of unilateral renal agenesis in the ... causes of oligohydramnios sequence have been linked to a number of other conditions and syndromes to include Down syndrome, ...
May 1994). "Evidence against DNA polymerase beta as a candidate gene for Werner syndrome". Human Genetics. 93 (5): 507-12. doi: ...
"Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer". Proceedings of the National Academy of ... lessons from pediatric cancer susceptibility syndromes". Journal of Clinical Oncology. 24 (23): 3799-808. doi:10.1200/JCO. ...
"Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer". Proc. Natl. Acad. Sci. U.S.A. 103 (23): ...
Futami K, Ishikawa Y, Goto M, Furuichi Y, Sugimoto M (2008). "Role of Werner syndrome gene product helicase in carcinogenesis ... "Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer". Proc. Natl. Acad. Sci. U.S.A. 103 (23): ... "Recapitulation of Werner syndrome sensitivity to camptothecin by limited knockdown of the WRN helicase/exonuclease". ...
Werner syndrome (WS) or Werners syndrome, also known as "adult progeria", is a rare, autosomal recessive disorder which is ... Werner syndrome is named after the German scientist Otto Werner. He identified the syndrome in four siblings observed with ... Otto Werner was the first to observe Werner syndrome in 1904 as a part of his dissertation research. As a German ... Progeroid syndromes, Syndromes affecting stature, Syndromes affecting bones, Syndromes affecting the nervous system, Diseases ...
Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Explore symptoms, ... medlineplus.gov/genetics/condition/werner-syndrome/ Werner syndrome. ... Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is ... Werner syndrome is estimated to affect 1 in 200,000 individuals in the United States. This syndrome occurs more often in Japan ...
By Jessica Lee SYLP student Born and raised in Saigon, Vietnam, she came to the United States all by herself when she was only 17 years old. With no extra money and knowing no Vietnamese people in the States, she learned to speak English and graduated from Nathan Hale High School only two years after […]. ...
Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ... Management guideline for Werner syndrome 2020 8. Calcification in tendons associated with Werner syndrome. Geriatr Gerontol Int ... encoded search term (Werner Syndrome) and Werner Syndrome What to Read Next on Medscape ... Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ...
Werner syndrome is a progeric syndrome characterized by premature atherosclerosis, diabetes, cancer, and death in humans. The ... Werner syndrome is a progeric syndrome characterized by premature atherosclerosis, diabetes, cancer, and death in humans. The ... Liver aging and pseudocapillarization in a Werner syndrome mouse model J Gerontol A Biol Sci Med Sci. 2014 Sep;69(9):1076-86. ...
Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ... Management guideline for Werner syndrome 2020 8. Calcification in tendons associated with Werner syndrome. Geriatr Gerontol Int ... encoded search term (Werner Syndrome) and Werner Syndrome What to Read Next on Medscape ... Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ...
Metabolic syndrome and female gender, but not methotrexate,… November 1, 2020 *Tonsillar fat herniation: A novel finding in ...
Recapitulation of Werner syndrome sensitivity to camptothecin by limited knockdown of the WRN helicase/exonuclease. / Bird, J.L ... Recapitulation of Werner syndrome sensitivity to camptothecin by limited knockdown of the WRN helicase/exonuclease. In: ... keywords = "Werner syndrome, WRN, RecQ, Camptothecin, Topoisomerase, RNAi, Ribozyme, Aging, Cancer",. author = "J.L.E. Bird and ... Recapitulation of Werner syndrome sensitivity to camptothecin by limited knockdown of the WRN helicase/exonuclease. ...
People with Werner syndrome also have an increased predisposition to cancers. The most common neoplasms in Werner syndrome are ... Researchers suggest that Werner syndrome is due to complete loss of function of the helicase protein encoded by the WRN gene. ... Individuals with Werner Syndrome have an abnormally slow growth rate, and there is cessation of growth at puberty. As a result ... Werner syndrome is caused by abnormal changes (mutations) in the WRN gene. More than 80 different mutations of the WRN gene ...
Werner Syndrome) Who Named It? C. W. Otto Werner Genetic Disorders: Werner Syndrome v ... after whom Werner syndrome, a form of ... such as Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndromes (RTS) and ... Werner syndrome (WS) Bloom syndrome ... Syndrome, Werner. Syndrome, Werners. Syndrome, Werners. Werners Syndrome. Werners Syndrome. Tree number(s):. C16.320.925. ... ... Werner SyndromeSyndromeAging, PrematureProgeriaBloom SyndromeRothmund-Thomson SyndromeGenomic InstabilityDown SyndromeMetabolic ...
Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ... encoded search term (Werner Syndrome) and Werner Syndrome What to Read Next on Medscape ... Barrios Sanjuanelo A, Munoz Otero C. [Atypical Werner syndrome: Atypical progeroid syndrome: A case report.]. An Pediatr (Barc) ... The Werner syndrome. A model for the study of human aging. Ann N Y Acad Sci. 2000 Jun. 908:167-79. [QxMD MEDLINE Link]. ...
WERNER SYNDROME. Category: Clinical Genetics Genomics. WRN GENE ANALYSIS Werner Syndrome is an adult onset progeroid disease. ... Werner Syndrome White cell enzymes whooping cough WNK4 Wolcott Rallison Syndrome WRN ZMPSTE24 β-glucosidase deficiency β-hCG ... Fanconi-Bickel Syndrome FASP Feingold Syndrome fetal FGD1 FGF23 FIPA first trimester screening FIT FIT; qFIT; occult blood flu ... Downs syndrome download EBP EBV Edwards syndrome EFTUD2 EGFR EIF2AK3 ENPP1 enterobius vermicularis epilepsy epileptic Epstein ...
Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ... encoded search term (Werner Syndrome) and Werner Syndrome What to Read Next on Medscape ... Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral ... Barrios Sanjuanelo A, Munoz Otero C. [Atypical Werner syndrome: Atypical progeroid syndrome: A case report.]. An Pediatr (Barc) ...
Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique. In: Annals of the New York Academy ... Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique. / Lowe, J.E.; Sheerin, Angela; ... Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique. Annals of the New York Academy of ... Werner syndrome (WS) is an inherited genetic disease in which individuals display the premature aging of a selected subset of ...
title = "Werner syndrome protein: Biochemical properties and functional interactions",. abstract = "Werner syndrome is a ... N2 - Werner syndrome is a premature aging syndrome displaying numerous signs and symptoms found in normal aging. The disease is ... AB - Werner syndrome is a premature aging syndrome displaying numerous signs and symptoms found in normal aging. The disease is ... Werner syndrome is a premature aging syndrome displaying numerous signs and symptoms found in normal aging. The disease is ...
Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR‐0379 (0.1%) was sprayed on skin ... The DESIGN‐R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two ... Results The reduction rate of ulcer size treated with 0.1% SR‐0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4 ... The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia ...
Werner syndrome. Other risk factors may include:. *previous radiation therapy. *exposure to certain chemicals, such as thorium ...
... which also includes the product of the Blooms syndrome gene (BLM). In this work, we show that WRN promotes the ATP-dependent ... Individuals affected by the autosomal recessive disorder Werners syndrome (WS) develop many of the symptoms characteristic of ... Werners syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. ... Werners syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. ...
Werner Syndrome Protein Is Regulated and Phosphorylated by DNA-dependent Protein Kinase. In: Journal of Biological Chemistry. ... Werner Syndrome Protein Is Regulated and Phosphorylated by DNA-dependent Protein Kinase. Journal of Biological Chemistry. 2001 ... Werner Syndrome Protein Is Regulated and Phosphorylated by DNA-dependent Protein Kinase. / Yannone, Steven M.; Roy, Sashwati; ... Yannone, S. M., Roy, S., Chan, D. W., Murphy, M. B., Huang, S., Campisi, J., & Chen, D. J. (2001). Werner Syndrome Protein Is ...
Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells. Maity J, Bohr VA, ... Mutations in WRN lead to premature aging, known as Werner syndrome (WS). ... His graduate thesis focused on the nuclear protein Werner (WRN) and autophagy. ...
Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells. eLife 8, e43333 (2019). ... Kategaya, L., Perumal, S. K., Hager, J. H. & Belmont, L. D. Werner Syndrome Helicase Is Required for the Survival of Cancer ...
Review of the literature found meningiomas associated with Werner syndrome occur about two times more frequently in men than in ... A 53-year-old man presented with a rare meningioma associated with Werner syndrome. Screening brain magnetic resonance (MR) ... Patients with meningioma associated with Werner syndrome should be carefully followed up to detect the occurrence of other ... Most meningiomas associated with Werner syndrome are benign, but are sometimes complicated with extracranial tumors such as ...
Werner syndrome. 2. 142 WT1. Transcription factor. Essential role in development.. Wilms tumors (pediatric kidney cancer). 1. ... One such syndrome, the Li-Fraumeni cancer family syndrome, is associated with a wide variety of cancers.98 In addition, several ... Cowden syndrome; increased risk of breast and thyroid cancer. 2. 139 RB1. Binds to, and inhibits, the E2F transcription factor ... 98Li-Fraumeni Syndrome. LFS - Genetic Information. OMIM, National Center for Biotechnology Information. Accessed 10/2/2010 [ ...
Li-Fraumeni syndrome;. *Werner syndrome (adult progeria);. *Nevoid basal cell carcinoma syndrome (Gorlin syndrome). ... Noonan syndrome;. *children born with high birth weights or larger than expected when born have increased risk of embryonal ... having AIDS (Acquired immune deficiency syndrome) and Epstein-Barr virus infection at the same time. ...
Name: Werner syndrome RecQ like helicase. Type: Gene. Species: Mus musculus (mouse) ...
Werner syndrome. *Tuberous sclerosis. Not everyone with risk factors will develop fibrosarcoma. Conversely, the absence of risk ...
This leads to Werners syndrome.. *CH9: This determines the blood group. It also has a role in disease we suffer. Skin cancer ... This causes Wardenburg syndrome.. *CH3: Contains evidences for the entire past history in the form of genes. Faulty VHL gene ... This leads to Marfans syndrome (position unknown).. *CH16: This contains memory. Faulty PKD1 gene causes cysts to form, which ... This leads to DiGeorge syndrome. Chromosome-22 plays an important role in immune system, mental disturbances and some types of ...
The elusive regulator must be very different to the genes that cause progeria and Werners syndrome, Walker says. The symptoms ... unlike the mutated versions in patients with Werners Syndrome and progeria. "That was the first thing we looked at," he said. ...
Children with Werner syndrome. These children have a higher risk of sarcoma, thyroid cancer, and melanoma. Werner syndrome is a ... Children with Li-Fraumeni syndrome. A child with Li-Fraumeni syndrome has a higher risk of sarcoma, including osteosarcoma, as ... People with Rothmund-Thomson syndrome. This group of people is more likely to develop osteosarcoma. Rothmund-Thomson syndrome ... Li-Fraumeni syndrome is a rare disorder of the p53 gene. That gene is responsible for getting rid of abnormal cells. ...
Werner and hutchinson-gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Bio. (2007) 8 ...
  • Kyng KJ, Bohr VA. Gene expression and DNA repair in progeroid syndromes and human aging. (medscape.com)
  • WS and several other progeroid syndromes are epigenetically distinct disorders. (medscape.com)
  • Progeroid syndromes a. (nih.gov)
  • Progeroid syndromes are rare disorders that cause premature aging and shorten life expectancy. (msdmanuals.com)
  • In progeroid syndromes, the aging process is greatly accelerated. (msdmanuals.com)
  • Thus, progeroid syndromes are not an exact model of accelerated aging. (msdmanuals.com)
  • There are several progeroid syndromes. (msdmanuals.com)
  • Progeroid Syndromes Certain disorders have some of the same effects as aging. (msdmanuals.com)
  • In contrast to progeroid syndromes, Down syndrome greatly impairs the central nervous system. (msdmanuals.com)
  • These findings provide new insight into progeroid syndromes and how to treat them, while also highlighting the importance of LINE-1 RNA in normal aging," says co-corresponding author Juan Carlos Izpisua Belmonte , a professor in Salk's Gene Expression Laboratory and director of the Altos Labs San Diego Institute of Science. (eurekalert.org)
  • Progeroid syndromes, which include Hutchinson-Gilford progeria syndrome and Werner syndrome, cause accelerated aging in children and adolescents. (eurekalert.org)
  • There are currently no effective treatments for progeroid syndromes. (eurekalert.org)
  • Izpisua Belmonte and his colleagues knew that one of the molecular signatures of both normal aging and progeroid syndromes is the altered overall organization of DNA. (eurekalert.org)
  • Izpisua Belmonte's team wondered whether they also changed in progeroid syndromes. (eurekalert.org)
  • The researchers studied cells derived from patients with progeroid syndromes and found that they had four to seven times more LINE-1 RNA than cells from healthy individuals. (eurekalert.org)
  • Targeting LINE-1 RNA may be an effective way to treat progeroid syndromes, as well as other age-related diseases that have been connected to LINE-1, including neuropsychiatric, eye, metabolic disorders and cancers," says Izpisua Belmonte, holder of the Roger Guillemin Chair. (eurekalert.org)
  • Werner syndrome is a condition that causes premature aging. (nih.gov)
  • Werner syndrome (WS) or Werner's syndrome, also known as "adult progeria", is a rare, autosomal recessive disorder which is characterized by the appearance of premature aging. (wikipedia.org)
  • He identified the syndrome in four siblings observed with premature aging, which he explored as the subject of his dissertation of 1904. (wikipedia.org)
  • Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss), wrinkling, prematurely aged faces with beaked noses, skin atrophy (wasting away) with scleroderma-like lesions, lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli (around ankles). (wikipedia.org)
  • Davis T, Wyllie FS, Rokicki MJ, Bagley MC, Kipling D. The role of cellular senescence in Werner syndrome: toward therapeutic intervention in human premature aging. (medscape.com)
  • Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. (nih.gov)
  • The diagnosis of Werner syndrome is established in a proband with the following cardinal signs: bilateral ocular cataracts, premature graying and/or thinning of scalp hair, characteristic dermatologic pathology, and short stature. (nih.gov)
  • Werner's syndrome is a rare autosomal recessive disease resulting in premature aging. (medscape.com)
  • The DNA Helicase Section was the first to discover a small molecule inhibitor of the WRN helicase, defective in the premature aging disease Werner syndrome. (nih.gov)
  • Mutations in WRN lead to premature aging, known as Werner syndrome (WS). (nih.gov)
  • BACKGROUND: Werner syndrome (WS) results from defects in the RecQ helicase (WRN) and is characterized by premature aging and accelerated tumorigenesis. (nih.gov)
  • Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by premature aging. (genetex.com)
  • Previous studies have shown that MSCs decrease in number and proliferative capacity as the body ages [ 10 ], as observed in the premature aging diseases including Werner syndrome and Hutchinson-Gilford premature aging syndrome, as well as in the aging mouse models [ 11 , 12 ]. (hindawi.com)
  • Evidence of the role that DNA repair plays in the aging process comes in part from studies of genetic disorders such as Werner's syndrome, an autosomal recessive disorder characterized by the premature appearance of many features of normal aging. (dermatologytimes.com)
  • There's a syndrome called Werner's syndrome that leads to premature aging. (oldpodcast.com)
  • Novel LMNA gene mutation in a patient with Atypical Werner's Syndrome. (medscape.com)
  • Werner's Syndrome with Hypertrophic Cardiomyopathy" by Zerrin KAPICIOĞLU, Sait KAPICIOĞLU et al. (tubitak.gov.tr)
  • Pregnancy complicated by Werner's syndrome. (nih.gov)
  • Successful outcome of pregnancy complicated by Werner's syndrome. (nih.gov)
  • Werner's syndrome combined with pseudo-Klinefelter's syndrome]. (nih.gov)
  • Among the skin manifestations of Werner's syndrome, dryness and atrophy, scleroderma-like appearance, beak-nose, hyperkeratosis over bone prominences, and chronic leg ulcers most often are present. (medscape.com)
  • 16. [Musculoskeletal complications of Werner's syndrome]. (nih.gov)
  • In tissue culture, the lifespan of fibroblasts from individuals with Werner's syndrome is markedly reduced compared to that of fibroblasts from normal individuals. (dermatologytimes.com)
  • Patients with Werner's syndrome have a mutation that abolishes the function of a helicase enzyme essential for DNA repair and for maintenance of telomeres at the end of chromosomes. (dermatologytimes.com)
  • Werner's syndrome is rare , though. (oldpodcast.com)
  • Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital mullerian anomaly consisting of uterus didelphys, hemivaginal septum, and unilateral renal agenesis [1,2]. (univpm.it)
  • Most authors reported cases of Herlyn-Werner-Wunderlich syndrome with prepuberal or postpuberal onset with cyclical abdominal pain and a vaginal mass (3-8). (univpm.it)
  • Introduction: Herlyn-Werner-Wunderlich Syndrome (HWWS) is a rare congenital anomaly of female urogenital tract caused by abnormalities in the development of the Mullerian ducts resulting in uterus didelphys, obstructed hemivagina, and associated ipsilateral renal anomaly. (ijsr.net)
  • The prevalence of rare cancers, such as meningiomas, are increased in individuals with Werner syndrome. (wikipedia.org)
  • Individuals with Werner syndrome develop normally until the end of the first decade. (nih.gov)
  • the mean age of death in individuals with Werner syndrome is 54 years. (nih.gov)
  • 20. RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. (nih.gov)
  • Inherited conditions that increase the risk of osteosarcoma are hereditary retinoblastoma, Li-Fraumeni syndrome, and Rothmund-Thomson, Bloom, and Werner syndromes. (dana-farber.org)
  • WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations. (medscape.com)
  • The net metabolic outcome in patients of diabetes with a syndrome or a condition (e.g., a with secondary diabetes thus depends on the direct or number of genetic syndromes). (nih.gov)
  • These genetic syndromes are caused by hereditary errors, called mutations, in the genetic code or DNA. (cancercenter.com)
  • Family cancer syndromes are disorders caused by gene defects (mutations) that people are born with (often inherited from a parent) that are linked to a high risk of getting certain cancers. (cancer.org)
  • 4. Severe metabolic disorders coexisting with Werner syndrome: a case report. (nih.gov)
  • Kudlow BA, Kennedy BK, Monnat RJ Jr. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. (medlineplus.gov)
  • Progeria can also refer to Hutchinson-Gilford syndrome , which is described as a lamin A gene defect and has onset early in life. (medscape.com)
  • Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome. (nih.gov)
  • Studying Werner syndrome to elucidate mechanisms and therapeutics of human aging and age-related diseases. (medscape.com)
  • This syndrome represents an important model for aging, possibly allowing improved understanding of mechanisms and therapeutics of human aging. (medscape.com)
  • The mutation in the WRN gene that causes Werner syndrome is autosomal and recessive, meaning that affected people must inherit a copy of the gene from each parent. (wikipedia.org)
  • A novel mutation of the WRN gene in a Chinese patient with Werner syndrome. (medscape.com)
  • Werner syndrome: clinical evaluation of two cases and a novel mutation. (medscape.com)
  • In young adults, mutation in the Werner syndrome (WS) gene is believed to be associated with clinical symptoms typically found in elderly individuals. (medscape.com)
  • Werner syndrome is caused by a mutation (change) in a gene involved in cell division. (medicalterminologydb.com)
  • Mitochondrial tRNA gene mutation syndromes f. (nih.gov)
  • Li-Fraumeni syndrome ( TP53 mutation ). (hoacny.com)
  • Gardner syndrome ( APC mutation). (hoacny.com)
  • Germline mutations in certain DNA helicase genes can cause cancer predisposition syndromes including the Bloom syndrome caused by BLM mutation [ 2 ] and the Werner syndrome caused by WRN mutation [ 3 ]. (hindawi.com)
  • Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome. (medscape.com)
  • 13. Bloom's syndrome workshop focuses on the functional specificities of RecQ helicases. (nih.gov)
  • For example, a higher prevalence of the disease has been observed in patients with Bloom's and Werner's syndromes, who have inherited mutations in specific genes that are involved in DNA replication, recombination, and repair. (cshlpress.com)
  • A case of Werner syndrome without metabolic abnormality: implications for the early pathophysiology. (medscape.com)
  • 19. A case of Werner syndrome with three primary lesions of malignant melanoma. (nih.gov)
  • In addition, people with Werner syndrome have an increased risk of developing cancer, especially thyroid and skin cancers. (nih.gov)
  • Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition. (medlineplus.gov)
  • People with Werner syndrome usually live into their late forties or early fifties. (medlineplus.gov)
  • 5. Oral squamous cell carcinoma arising in a patient with Werner syndrome. (nih.gov)
  • 18. Werner syndrome and mutations of the wrn and LMNA genes in France. (nih.gov)
  • Werner syndrome, a hereditary syndrome, begins in adolescence or early adult life. (msdmanuals.com)
  • Genetic conditions that increase cancer risks are called hereditary cancer syndromes. (cancercenter.com)
  • There is a wide variety of hereditary cancer syndromes linked to increased risk of developing pancreatic cancer, including those below. (cancercenter.com)
  • The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA. (medlineplus.gov)
  • Mutations in the WRN gene often lead to the production of an abnormally short, nonfunctional Werner protein. (medlineplus.gov)
  • Evidence also suggests that the altered protein is broken down more quickly in the cell than the normal Werner protein. (medlineplus.gov)
  • Cells with an altered Werner protein may divide more slowly or stop dividing earlier than normal, causing growth problems. (medlineplus.gov)
  • Lee JW, Harrigan J, Opresko PL, Bohr VA. Pathways and functions of the Werner syndrome protein. (medlineplus.gov)
  • Molecular interactions of the Werner syndrome protein / Robert M. Brosh. (nih.gov)
  • His graduate thesis focused on the nuclear protein Werner (WRN) and autophagy. (nih.gov)
  • 8. Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma. (nih.gov)
  • Results suggest that the RNase D family, which includes Werner syndrome protein and the 100 kDa antigenic component of the human polymyositis scleroderma (PMSCL) autoantigen, is a 3'-->5' exoribonuclease structurally and functionally related to the 3'-->5' exodeoxyribonuclease domain of DNA polymerases. (embl.de)
  • Werner syndrome patients are at increased risk for several other diseases, many associated with aging. (wikipedia.org)
  • T he overall objective of this project is to further the validation and development of tools for the therapeutic application of the GSE24-2 fragment for the treatment of various diseases, including dyskeratosis congenita, Werner syndrome, idiopathic pulmonary fibrosis, aplastic anaemia, ulcerative colitis and skin ageing as well as obtaining immortal human cell lines. (fundacionareces.es)
  • Werner syndrome (WS) is an autosomal recessive disorder that affects connective tissue throughout the body. (medscape.com)
  • Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations. (medscape.com)
  • Radiotherapy is contraindicated in this radiosensitivity syndrome. (medscape.com)
  • Aggarwal M, Sommers JA, Shoemaker RH, Brosh RM Jr., Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. (nih.gov)
  • Targeted long-read sequencing identifies missing pathogenic variants in unsolved Werner syndrome cases. (medscape.com)
  • The International Registry of Werner Syndrome has identified biallelic pathogenic variants in 179/188 cases of classical WS. (nih.gov)
  • Pirzio LM, Pichierri P, Bignami M, Franchitto A. Werner syndrome helicase activity is essential in maintaining fragile site stability. (medscape.com)
  • Children with PTEN hamartoma syndrome are predisposed to the cancers listed above as well as intestinal polyps. (medscape.com)
  • Werner syndrome patients often have skin that appears shiny and tight, and may also be thin or hardened. (wikipedia.org)
  • Other associated skin conditions include ulcers, which are very difficult to treat in Werner syndrome patients, and are caused in part by decreased potential of skin cells for replication. (wikipedia.org)
  • Ethnic-Specific WRN Mutations in South Asian Werner Syndrome Patients: Potential Founder Effect in Patients with Indian or Pakistani Ancestry. (medscape.com)
  • The mean survival for patients with Werner syndrome (WS) is 46 years. (medscape.com)
  • Between 1904 and 2008, researchers found that approximately 75% of patients with Werner syndrome (WS) worldwide were of Japanese descent. (aging-us.org)
  • La culture de type classique a permis d'identifier Neissera meningitidis chez 37 (18,9 %) des 196 patients ayant des symptômes et des signes cliniques de méningite, ce qui a ensuite été confirmé par réaction en chaîne par polymérase. (who.int)
  • Patients with WDHA syndrome may initially have an indolent course, or the disease may masquerade as other, more common conditions, leading to a delay in the diagnosis. (medscape.com)
  • Hypercalcemia occurs in 25-76% of patients with WDHA syndrome. (medscape.com)
  • Nearly 6% of these patients have associated MEN-1 syndrome with resultant hypercalcemia secondary to hyperparathyroidism. (medscape.com)
  • Cite this: Cutaneous Signs and Syndromes Associated With Internal Malignancies - Medscape - Mar 01, 2005. (medscape.com)
  • Severe to extreme insulin resistance syndromes b. (nih.gov)
  • Otto Werner originally defined Werner syndrome (WS) in 1904 on the basis of sclerodermalike, thin, tight skin and bilateral cataracts. (medscape.com)
  • When Do Symptoms of Werner syndrome Begin? (nih.gov)
  • Researchers do not fully understand how WRN mutations cause the signs and symptoms of Werner syndrome. (medlineplus.gov)
  • The parents of an individual with Werner syndrome each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. (medlineplus.gov)
  • Goto M, Ishikawa Y, Sugimoto M, Furuichi Y. Werner syndrome: a changing pattern of clinical manifestations in Japan (1917~2008). (medscape.com)
  • Werner syndrome is named after the German scientist Otto Werner. (wikipedia.org)
  • A large percentage of cases are associated with other intracranial anomalies, like aqueductal stenosis, other neural tube defects, Chiari malformations, Dandy-Walker syndrome, posterior fossa cysts, alobar oloprosencephaly and polymicrogyria. (jpgo.org)
  • At puberty, growth stops and adults with Werner syndrome are typically shorter than average. (nih.gov)
  • The syndrome typically develops within 24 hours after surgery and is characterized by corneal edema and accumulation of white cells in the anterior chamber of the eye. (cdc.gov)
  • Barrios Sanjuanelo A, Munoz Otero C. [Atypical Werner syndrome: Atypical progeroid syndrome: A case report. (medscape.com)
  • Case report of a long-surviving Werner syndrome patient with severe aortic valve stenosis. (medscape.com)
  • Werner syndrome (WS) is an autosomal recessive progeroid syndrome caused by variants in WRN . (nih.gov)
  • 1. Type A syndrome--classic and variants c. (nih.gov)
  • Davis T, Brook AJ, Rokicki MJ, Bagley MC, Kipling D. Evaluating the Role of p38 MAPK in the Accelerated Cell Senescence of Werner Syndrome Fibroblasts. (medscape.com)
  • Early detection and management can prevent the later complications of these syndrome. (ijsr.net)
  • In this new study, researchers from Japan investigated the molecular mechanisms of subcutaneous fat dysfunction in Werner syndrome. (aging-us.org)
  • Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. (medlineplus.gov)
  • Martin GM, Poot M, Haaf T. Lessons for aging from Werner syndrome epigenetics. (medscape.com)
  • Vitamin C restores healthy aging in a mouse model for Werner syndrome. (medscape.com)
  • 7. Alström syndrome (obesity, retinitis pigmentosa, deafness) e. (nih.gov)
  • Some family cancer syndromes increase a person's risk of developing soft tissue sarcomas. (cancer.org)
  • How much these conditions increase the risk of cancer and where in the body the cancer develops are different, depending on which syndrome you have. (cancercenter.com)
  • The possible early presentation of this syndrome should be suspected in all neonates (females) with renal agenesia confirmed postnatally or with prenatal diagnosis. (univpm.it)
  • The diagnosis of WDHA syndrome requires evidence of a state of hormonal excess. (medscape.com)
  • This syndrome occurs more often in Japan, affecting 1 in 20,000 to 1 in 40,000 people. (medlineplus.gov)
  • By the early 20s-30s, people with this syndrome develop conditions usually associated with more advanced ages. (nih.gov)
  • Letter to the editor: periodontal conditions in Werner syndrome. (nih.gov)
  • Early identification and treatment of acute HIV syndrome may halt disease progression and restore immunocompetence. (aafp.org)
  • Hisama FM, Kubisch C, Martin GM, Oshima J. Clinical utility gene card for: Werner syndrome. (medscape.com)