Novel Mutations in the ZEB1 Gene Identified in Czech and British Patients With Posterior Polymorphous Corneal Dystrophy
Novel Mutations in the ZEB1 Gene Identified in Czech and British Patients With Posterior Polymorphous Corneal Dystrophy
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DOI：
10.1002/humu.9495
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发表时间：
2007-06-01
期刊：
影响因子：
3.9
通讯作者：
Bhattacharya, Shomi S.
中科院分区：
文献类型：
--
作者：
Liskova, Petra;Tuft, Stephen J.;Bhattacharya, Shomi S.
我们描述了在患有后部多形性角膜营养不良（PPCD）的六个不相关的捷克和四个不相关的英国家庭中寻找突变的情况；一种相对罕见的眼部疾病。通过 DNA 测序筛选了先前报道与该疾病发病机制有关的所有三个基因（VSX1、COL8A2 和 ZEB1/TCF8）的编码外显子和内含子/外显子边界。在四个家族中发现了四种新的致病突变；位于 10p11.2 的 ZEB1 基因的外显子 7 内有两处缺失、一处无意义和一处重复。我们还对捷克患者进行了基因分型，以测试创始人单倍型以及我们之前描述的 20p11.2 基因座是否缺乏疾病分离。尽管没有进行系统的临床检查，但我们的调查并不支持 ZEB1 变化与自我报告的非眼部异常之间的关联。在其余 6 个家族中，没有发现引起疾病的突变，这表明尚未确定的基因可能与 PPCD 有关。
We describe the search for mutations in six unrelated Czech and four unrelated British families with posterior polymorphous corneal dystrophy (PPCD); a relatively rare eye disorder. Coding exons and intron/exon boundaries of all three genes (VSX1, COL8A2, and ZEB1/TCF8) previously reported to be implicated in the pathogenesis of this disorder were screened by DNA sequencing. Four novel pathogenic mutations were identified in four families; two deletions, one nonsense, and one duplication within exon 7 in the ZEB1 gene located at 10p11.2. We also genotyped the Czech patients to test for a founder haplotype and lack of disease segregation with the 20p11.2 locus we previously described. Although a systematic clinical examination was not performed, our investigation does not support an association between ZEB1 changes and self reported non-ocular anomalies. In the remaining six families no disease causing mutations were identified thereby indicating that as yet unidentified gene(s) are likely to be responsible for PPCD.