Localization of a gene for Duane retraction syndrome to chromosome 2q31
Localization of a gene for Duane retraction syndrome to chromosome 2q31
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DOI：
10.1086/302656
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发表时间：
1999-12-01
影响因子：
9.8
通讯作者：
Stout, JT
中科院分区：
文献类型：
--
作者：
Appukuttan, B;Gillanders, E;Stout, JT
Duane挛缩综合征（DRS）是一种先天性眼动障碍，其特征是颅神经VI（外展神经）不能正常发育，导致外展受限或无外展，内收受限，内收时睑裂变窄，眼球内收。DRS在普通人群中的患病率约为0.1%，占所有斜视病例的5%。未确诊的儿童DRS可导致弱视，一种永久性的无法矫正的视力丧失。研究了一个常染色体显性DRS的大家族，并检测了遗传连锁。在排除先前与DRS相关的候选区域后，使用高多态性微卫星标记进行全基因组搜索，并在染色体2q31上获得了显著的连锁证据（D2S2314最大LOD评分为11.73，最大重组分数为0.0）。单倍型分析表明，受影响的基因位于标记D2S2330和D2S364之间17.8 cm的区域。在这两个位点之间没有发现有标记的重组。链接区域包含同源盒D基因簇。在受影响个体和对照个体中，对这组基因中已知参与后脑发育的三个基因进行了测序。这些基因的编码序列是正常的，或者有不太可能导致DRS表型的遗传改变。确定与DRS有关的基因可能有助于提高对早期脑神经发育的理解。
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 similar to 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.