Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration
Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration
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DOI：
10.1016/s0896-6273(00)80423-7
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发表时间：
1997-12-01
期刊：
影响因子：
16.2
通讯作者：
Zack, DJ
中科院分区：
文献类型：
--
作者：
Swain, PK;Chen, SM;Zack, DJ
Crx 是一种新型配对样同源域蛋白，主要在视网膜感光器和松果体细胞中表达。其基因已被定位到染色体 19q13.3，这是常染色体显性锥杆营养不良 (CORDII) 的疾病位点。对来自常染色体显性 CORD 家族的先证者的分析显示，CRX 同源域的第三个残基存在 Arg41Trp 取代。该序列变化与疾病表型共分离，并且在 247 名正常对照中未检测到。含有 Arg41Trp 取代的重组 CRX 同源域显示 DNA 结合活性降低。对另外 169 个 CORD 先证者的分析发现了三个额外的 CRX 序列变异（Arg41Gln、Val242Met 和密码子 196/7 中的 4 bp 缺失），这些变异在对照中未发现。该数据表明，CRX 基因的突变与光感受器变性有关，并且 Crx 蛋白对于维持正常的视锥细胞和视杆细胞功能是必需的。
Crx is a novel paired-like homeodomain protein that is expressed predominantly in retinal photoreceptors and pinealocytes. Its gene has been mapped to chromosome 19q13.3, the site of a disease locus for autosomal dominant cone-rod dystrophy (CORDII). Analysis of the proband from a family with autosomal dominant CORD revealed an Arg41Trp substitution in the third residue of the CRX homeodomain. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. Recombinant CRX homeodomain containing the Arg41Trp substitution showed decreased DNA binding activity. Analysis of another 169 CORD probands identified three additional CRX sequence variations (Arg41Gln, Val242Met, and a 4 bp deletion in codons 196/7) that were not found among the controls. This data suggests that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function.