PVRL4 基因突变导致先天性外胚层发育不良并指（趾）畸形综合征（EDSS1）。

Mutation in PVRL4 gene encoding nectin-4 underlies ectodermal-dysplasia-syndactyly syndrome (EDSS1).

机构信息

Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

出版信息

J Hum Genet. 2011 May;56(5):352-7. doi: 10.1038/jhg.2011.18. Epub 2011 Feb 24.

DOI:10.1038/jhg.2011.18

Abstract

Ectodermal-dysplasia-syndactyly syndrome (EDSS1) is a rare form of ectodermal dysplasia (ED), affecting skin and its appendages mainly hair, teeth and nails. In the present study, we have investigated a large consanguineous Pakistani family with 10 individuals showing features of EDSS1. Human genome was screened using highly polymorphic microsatellite markers to identify the gene causing EDSS1. The disease locus for EDSS1 was assigned to chromosome 1q23.1-q23.3. This region corresponds to 5.63 Mb according to the sequenced based physical map (Build 36.2) of the human genome and flanked by markers D1S1653 and D1S1677. A maximum two-point LOD score of 5.05 was obtained with the marker D1S484. Sequence analysis revealed a homozygous missense mutation (c.635C>G; p.Pro212Arg) in the recently reported PVRL4 gene causing EDSS1. The involvement of mutant nectin-4 in causing EDSS1 may open up interesting prospectives into the role of cell adhesion molecules in causing syndromic forms of EDs.

摘要

外胚层发育不良并指（趾）综合征（EDSS1）是一种罕见的外胚层发育不良（ED）形式，主要影响皮肤及其附属物，包括毛发、牙齿和指甲。在本研究中，我们调查了一个有 10 名个体表现出 EDSS1 特征的大型巴基斯坦近亲家族。使用高度多态性微卫星标记对人类基因组进行了筛选，以鉴定导致 EDSS1 的基因。EDSS1 的疾病基因座被分配到染色体 1q23.1-q23.3。根据人类基因组的测序物理图谱（构建 36.2），该区域对应 5.63 Mb，由标记 D1S1653 和 D1S1677 侧翼。与标记 D1S484 获得的最大两点 LOD 得分为 5.05。序列分析显示，最近报道的 PVRL4 基因中存在纯合错义突变（c.635C>G;p.Pro212Arg），导致 EDSS1。突变 nectin-4 参与导致 EDSS1 的可能性为细胞黏附分子在导致综合征形式的 ED 中的作用开辟了有趣的前景。