title: Localization of a gene for Duane retraction syndrome to chromosome 2q31.
abstract: 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.
authors.affiliation: Division of Ophthalmology, Childrens Hospital Los Angeles, Los Angeles, CA, 90027, USA.
authors.forename: B
authors.initials: B
authors.lastname: Appukuttan
authors.forename: E
authors.initials: E
authors.lastname: Gillanders
authors.forename: S H
authors.initials: SH
authors.lastname: Juo
authors.forename: D
authors.initials: D
authors.lastname: Freas-Lutz
authors.forename: S
authors.initials: S
authors.lastname: Ott
authors.forename: R
authors.initials: R
authors.lastname: Sood
authors.forename: A
authors.initials: A
authors.lastname: Van Auken
authors.forename: J
authors.initials: J
authors.lastname: Bailey-Wilson
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: R J
authors.initials: RJ
authors.lastname: Patel
authors.forename: C M
authors.initials: CM
authors.lastname: Robbins
authors.forename: M
authors.initials: M
authors.lastname: Chung
authors.forename: G
authors.initials: G
authors.lastname: Annett
authors.forename: K
authors.initials: K
authors.lastname: Weinberg
authors.forename: M S
authors.initials: MS
authors.lastname: Borchert
authors.forename: J M
authors.initials: JM
authors.lastname: Trent
authors.forename: M J
authors.initials: MJ
authors.lastname: Brownstein
authors.forename: J T
authors.initials: JT
authors.lastname: Stout
mesh_terms: D019943:Amino Acid Substitution; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004370:Duane Retraction Syndrome / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008800:Mexico; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D019683:Penetrance
chemical_list: D003062:Codon