Localization of a gene for Duane retraction syndrome to chromosome 2q31. (1/58)

Duane retraction syndrome (DRS) is a congenital eye-movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, restricted adduction, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. DRS has a prevalence of approximately 0.1% in the general population and accounts for 5% of all strabismus cases. Undiagnosed DRS in children can lead to amblyopia, a permanent uncorrectable loss of vision. A large family with autosomal dominant DRS was examined and tested for genetic linkage. After exclusion of candidate regions previously associated with DRS, a genomewide search with highly polymorphic microsatellite markers was performed, and significant evidence for linkage was obtained at chromosome 2q31 (D2S2314 maximum LOD score 11.73 at maximum recombination fraction. 0). Haplotype analysis places the affected gene in a 17.8-cM region between the markers D2S2330 and D2S364. No recombinants were seen with markers between these two loci. The linked region contains the homeobox D gene cluster. Three of the genes within this cluster, known to participate in hindbrain development, were sequenced in affected and control individuals. Coding sequences for these genes were normal or had genetic alterations unlikely to be responsible for the DRS phenotype. Identifying the gene responsible for DRS may lead to an improved understanding of early cranial-nerve development.  (+info)

A case of congenital inverse Duane's retraction syndrome. (2/58)

Inverse Duane's retraction syndrome is very uncommon. Congenital cases are even more unusual. A 6-year-old girl with convergent squint along with severe restriction on abduction is described. On attempted abduction, a narrowing of the palpebral fissure, upshoot and retraction of the eyeball were observed. Brain and orbit MRI demonstrated no intracranial or intraorbital mass, fracture, or entrapment of the medial rectus. Forced duction test was strongly positive. The primary lesion was found to be a tight medial rectus with shortening and soft tissue contracture. Surgical tenotomy of the medial rectus led to successful postoperative motility, but some limitation at full adduction and abduction persisted. This is a case reported with congenital medial rectus shortening, suggesting that this condition may be one of the etiologies of the rare inverse Duane's retraction syndrome.  (+info)

Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb. (3/58)

Duane syndrome (MIM 126800) is an autosomal dominant disorder characterised by primary strabismus and other ocular anomalies, associated with variable deficiency of binocular sight. We have recently identified a < 3 cM smallest region of deletion overlap (SRO) by comparing interstitial deletions at band 8q13 in two patients (one described by Vincent et al, 1994, and the other by Calabrese et al, 1998). Here we report on another patient with Duane syndrome carrying a reciprocal translation t(6;8)(q26;q13). FISH and PCR analyses using a YAC contig spanning the SRO narrowed the Duane region to a < 1 cM interval between markers SHGC37325 and W14901. In addition, the identification and mapping of two PAC clones flanking the translocation breakpoint, allowed us to further narrow the critical region to about 40 kb. As part of these mapping studies, we have also refined the map position of AMYB, a putative candidate gene, to 8q13, centromeric to Duane locus. AMYB is expressed in brain cortex and genital crests and has been previously mapped to 8q22.  (+info)

Increased binocular enhancement of contrast sensitivity and reduced stereoacuity in Duane syndrome. (4/58)

PURPOSE: To compare the binocular enhancement of contrast sensitivity and stereoacuity in patients with Duane syndrome and normal subjects. METHODS: Monocular and binocular contrast sensitivity functions were determined using a two-alternative, forced-choice method in 14 patients with Duane syndrome and 14 normal subjects. Monocular and binocular log minimum angle of resolution (logMAR) acuities were measured, and stereoacuity was determined using the Titmus and TNO stereotests. RESULTS: In the patients with Duane syndrome, the binocular enhancement of contrast sensitivity was increased across all spatial frequencies, although stereoacuity was reduced compared to that of the normal subjects. The increased enhancement was caused by a reduction in monocular contrast sensitivity rather than an increase in binocular contrast sensitivity. The patients with Duane syndrome also showed a generalized reduction of contrast sensitivity at high spatial frequencies. CONCLUSIONS: It is suggested that the combination of reduced stereoacuity and increased binocular enhancement of contrast sensitivity seen in Duane syndrome can be explained by a partial loss of binocular cortical cells, caused by intermittent misalignment of the eyes during early visual development.  (+info)

Reduced binocular beat visual evoked responses and stereoacuity in patients with Duane syndrome. (5/58)

PURPOSE: To study the effects that the abnormal eye movements of patients with Duane retraction syndrome have on the development of binocular function. METHODS: Pattern reversal visual evoked responses (VEPs) to 15-minutes-of-arc and 60-minutes-of-arc checks and binocular beat VEPs to diffuse sinusoidally modulated 18- and 20-Hz stimuli were recorded in 10 patients with Duane retraction syndrome who maintain binocular function by using an abnormal head posture. Visual acuity, stereoacuity, and eye movements were measured. The results have been compared to those from 10 normal subjects. RESULTS: The patients with Duane retraction syndrome had reduced stereoacuity compared to the normal control group (TNO mean, 82.5 seconds of arc compared to 37.5 seconds of arc; Titmus mean, 143 seconds of arc compared to 44 seconds of arc). The binocular beat VEPs showed a significantly reduced difference beat response at 2 Hz in the patients with Duane syndrome compared to normal subjects (mean signal-to-noise ratio 2.40 +/- 1.05 compared to 4.30 +/- 2.66; t = 2.21, df = 18, P < 0.05). Binocular enhancement of the P100 pattern reversal amplitude to 15-minute checks was increased in these patients, because of a reduction of the monocular P100 amplitudes compared to the normal group. CONCLUSIONS: Patients with Duane syndrome who maintain binocular function using an abnormal head posture have reduced stereoacuity and show electrophysiological evidence of reduced cortical binocular interaction.  (+info)

Okihiro syndrome is caused by SALL4 mutations. (6/58)

Okihiro syndrome refers to the association of forearm malformations with Duane syndrome of eye retraction. Based on the reported literature experience, clinical diagnosis of the syndrome can be elusive, owing to the variable presentation in families reported. Specifically, there is overlap of clinical features with other conditions, most notably Holt-Oram syndrome, a condition resulting from mutation of the TBX5 locus and Townes-Brocks syndrome, known to be caused by mutations in the SALL1 gene. Arising from our observation of several malformations in Okihiro syndrome patients which are also described in Townes-Brocks syndrome, we postulated that Okihiro syndrome might result from mutation of another member of the human SALL gene family. We have characterized the human SALL4 gene on chromosome 20q13.13-q13.2. Moreover, we have identified literature reports of forelimb malformations in patients with cytogenetically identifiable abnormalities of this region. We here present evidence in 5 of 8 affected families that mutation at this locus results in the Okihiro syndrome phenotype.  (+info)

Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. (7/58)

Duane syndrome is a congenital eye movement disorder characterized most typically by absence of abduction, restricted adduction, and retraction of the globe on attempted adduction. Duane syndrome can be coinherited with radial ray anomalies as an autosomal dominant trait, referred to as "Okihiro syndrome" or "Duane radial ray syndrome" (DRRS). We ascertained three pedigrees with DRRS and mapped their disease gene to a 21.6-cM region of chromosome 20 flanked by markers D20S888 and D20S102. A new member of the SAL family of proposed C(2)H(2) zinc finger transcription factors, SALL4, falls within the region. Mutation analysis of SALL4 in the three pedigrees revealed one nonsense and two frameshift heterozygous mutations. SALL4 represents the first identified Duane syndrome gene and the second malformation syndrome resulting from mutations in SAL genes and likely plays a critical role in abducens motoneuron development.  (+info)

A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a duane syndrome patient. (8/58)

PURPOSE: To identify the gene disrupted by a de novo reciprocal balanced translocation t(6;8)(q26;q13) in a patient with Duane retraction syndrome (DURS). The break point in chromosome arm 8q is positioned within the DURS1 critical region. METHODS: Fluorescence in situ hybridization (FISH) analysis using cosmid and BAC clones covering the DURS1 locus was performed to define the break point position and its relationship with expressed sequence tags (ESTs) in the region. Once the interrupted gene was identified, the full-length cDNA was sequenced and the genomic organization defined. Eighteen patients with sporadic DURS without cytogenetic abnormalities involving the DURS1 region were screened for point mutations in the candidate DURS1 gene. RESULTS: A carboxypeptidase gene (CPAH) was directly interrupted between the first and second exons in a patient with DURS who carried a de novo reciprocal balanced translocation t(6;8)(q26;q13) involving the DURS1 region on chromosome arm 8q13. The gene was transcribed in at least two alternative mRNA forms, with different start and stop codons. CONCLUSIONS: The CPAH gene was interrupted in a patient with DURS carrying a translocation break point in the DURS1 region on chromosome 8q13. CPAH is therefore a likely candidate for this abnormality, even if the possibility that other genes are involved, either by direct effects on transcription units present in the first CPAH intron or by position effects, cannot be ruled out. Functional studies of the influence of this gene on the morphogenesis of eye muscles and their innervation may clarify this question.  (+info)

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