Complex cytogenetic rearrangements at the DURS1 locus in syndromic Duane retraction syndrome (original) (raw)
Localization of a Gene for Duane Retraction Syndrome to Chromosome 2q31
The American Journal of Human Genetics, 1999
Duane retraction syndrome (DRS) is a congenital eyemovement 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 ∼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.
Duane Retraction Syndrome Associated with a Small X Chromosome Deletion
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2016
This report describes the genetic evaluation of a girl with bilateral Duane retraction syndrome (DRS), cleft palate, and mildly reduced hearing who was found by high-resolution array-comparative genomic hybridization (array CGH) to have a chromosomal anomaly involving a single gene known to be involved in muscle development. The study was approved by the Institutional Review Board of the
Duane Syndrome in the Setting of Chromosomal Duplications
American Journal of Ophthalmology, 2010
To describe the clinical findings in 3 patients with Duane syndrome and 3 different chromosomal duplications that may indicate the location of genes involved in the pathogenesis of this ocular motility disorder. • DESIGN: Observational case series. • METHODS: SETTING: Clinical practice. PATIENT OR STUDY POPULATION: Three patients with Duane syndrome and chromosomal duplications from the clinical practice of 1 of the authors. OBSERVATION PROCEDURES: Chart review and retrieval of clinical data and results of pertinent clinical tests, in this case chromosomal studies. MAIN OUTCOME MEASURE: Reporting of details of clinical findings and duplicated chromosomal regions. • RESULTS: Two patients had unilateral type I Duane syndrome and 1 had bilateral type I Duane syndrome. Two had cognitive delay, and all 3 had other systemic abnormalities, including a variety of congenital malformations. The chromosomal abnormalities that were detected using microarray analysis were 2q13(RP11-20G1,RP11-461N11) ؋ 3, 10q24.2q26.3(101,532,585-135,284, 169) ؋ 3, 20q13.12 (44,796,613-44,945, 818) ؋ 3, and 22q11.1q11.22(RP11-701M12, RP11-71G19) ؋ 3. • CONCLUSIONS: Patients with Duane syndrome and associated congenital malformations or developmental delay should be evaluated for the presence of underlying chromosomal duplications. The regions of chromosomes 2, 10, and 22 that we report may harbor genes involved in the pathogenesis of Duane syndrome.
European Journal of Human Genetics, 1998
Duane syndrome (MIM126800) is an autosomal dominant disease responsible for 1% of all strabismus cases and has been related to a 8q12-13 contiguous gene syndrome. We report on an insertion of chromosome region 8q13-q21.2 on to band 6q25 in a patient presenting with Duane syndrome, mental retardation, and other dysmorphisms. FISH analysis using chromosome 8 radiation hybrid LIA2L indicated a concurrent deletion within the 8q rearranged region. These results were corroborated by STR-PCR analysis and FISH using YAC contig WC8.8 disclosed a deletion in 8q13. Comparison of the two known patients with Duane syndrome associated with deletion of 8q identifies a small region of overlap (SRO) of < 3 cM extending from D8S533 and D8S1767 in which a Duane syndrome locus is assigned. In addition YAC analysis in our patient showed that 8q rearrangement was rather complex since 8q deletion and insertion occurred in two distinct segments separated by a region which maintained its location on 8q.
American Journal of Medical Genetics, 2009
We report on a patient with severe mental retardation, dysmorphic features as well as juvenile idiopathic arthritis. G-banding indicated two independent karyotypic anomalies in this patient: an interstitial deletion del(X)(p21p22.3) and a rearrangement involving chromosomes 1 and 7, which represents a direct insertion, ins(7;1) (q36;p13.2p31.2). Non-random inactivation of the paternally derived del(X) chromosome was observed in blood lymphocytes and fibroblasts. High resolution analysis of the rearrangement involving chromosomes 1 and 7 subsequently revealed the additional submicroscopic deletion of at least 5 Mb at the 1p13.2 breakpoint. The deletion occurred on the paternal chromosome and encompasses the PTPN22 gene, already known to be associated with juvenile idiopathic arthritis. Our findings underline the importance of closely investigating the breakpoint regions of apparently balanced rearrangements in patients with abnormal phenotypes since complex chromosomal rearrangements (CCRs) may turn out to be unbalanced.
A case of 9p deletion syndrome with Duane retraction syndrome
Journal of Pediatric Genetics, 2015
The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, and a long philtrum) and psychomotor retardation. Here we report a child with chromosome 9p deletion with Duane retraction syndrome, which has never been reported in the literature before.