TY - JOUR
T1 - Localization of a gene for Duane retraction syndrome to chromosome 2q31
AU - Appukuttan, Binoy
AU - Gillanders, Elizabeth
AU - Juo, Suh Hang
AU - Freas-Lutz, Diana
AU - Ott, Sandra
AU - Sood, Raman
AU - Van Auken, Ann
AU - Bailey-Wilson, Joan
AU - Wang, Xiaoguang
AU - Patel, Reshma J.
AU - Robbins, Christiane M.
AU - Chung, Mina
AU - Annett, Geralyn
AU - Weinberg, Kenneth
AU - Borchert, Mark S.
AU - Trent, Jeffrey M.
AU - Brownstein, Michael J.
AU - Timothy Stout, J.
PY - 1999
Y1 - 1999
N2 - 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 ≃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 17.8cM 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.
AB - 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 ≃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 17.8cM 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.
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U2 - 10.1086/302656
DO - 10.1086/302656
M3 - Article
C2 - 10577917
AN - SCOPUS:0033358519
SN - 0002-9297
VL - 65
SP - 1639
EP - 1646
JO - American journal of human genetics
JF - American journal of human genetics
IS - 6
ER -