应用全外显子测序对有汗性外胚叶发育不良家系致病基因突变筛查

Screening for pathogenic mutations of Hidrotic ectodermal dysplasia by whole exome sequencing in a Chinese family study

目的筛查外胚叶发育不良(HED)家系的致病基因。方法收集HED家系的临床资料及DNA标本,通过全外显子测序及Sanger测序,筛查HED家系的致病基因。结果家系中患儿为完全表型,具有典型HED三联症表现,其母亲及舅舅为非完全表型。患儿行全外显子测序发现其GBJ2基因发生突变,而既往报道的HED致病基因GBJ6的四个位点(G11R、V37E、D50N、A88V)均无突变;GJA1基因的V41L位点,以及GJB2的R127H、F191L位点未发现突变。Sanger测序进一步确认,GBJ2在患儿、母亲、外婆中发生突变,突变位点均为rs80338943,又名235delC,而舅舅未发现突变。结论该结果提示GJB6并不是HED必需的或者唯一致病基因。而GJB2基因235delC位点的突变与HED的关系有待进一步确认。本研究为探明HED疾病的相关基因及分子机制提供新的线索。

Objective Screening for pathogenic mutations of ectodermal dysplasia（HED）in a Chinese family.Methods The clinical data and DNA samples of HED pedigrees were collected.The pathogenic genes of HED pedigrees were screened by whole exome sequencing and Sanger sequencing.Results In this Chinese family,the child had complete HED phenotype with typical manifestations,and the mother and uncle were incompletely phenotype.In the child,whole exome sequencing found a mutation in GBJ2 gene,but no mutation in GBJ6 gene and GJA1 gene,which two were reported before.Sanger sequencing further confirmed the GBJ2 mutations were found in children,mother and grandmother.The mutation sites are rs80338943,also known as 235 delC.However,uncle did not find GBJ2 mutations.Conclusion This result suggests that GJB6 mutation is not an essential for HED.The relationship of GJB2 gene（235 delC）mutation and HED needs further explored.This study provides new clues to understand the pathogenic genes of HED disease.