单纯型大疱性表皮松解症患儿的角蛋白5基因突变研究  

Mutation analysis of keratin 5 gene in a child with epidermolysis bullosa simplex

作　　者：刘芙蓉[1] 王兴[1] 郝胜菊[1] 张庆华[1] 马盼盼 周秉博 张钏[1] 王石凡 LIU Furong;WANG Xing;HAO Shengju;ZHANG Qinghua;MA Panpan;ZHOU Bingbo;ZHANG Chuan;WANG Shifan(Center of Medical Genetics,Gansu Provincial Maternity and Child-care Hospital,Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases,Lanzhou 730050,China)

机构地区：[1]甘肃省妇幼保健院医学遗传学中心、甘肃省出生缺陷与罕见病临床研究中心,甘肃兰州730050

出　　处：《临床皮肤科杂志》2024年第1期15-18,共4页Journal of Clinical Dermatology

基　　金：甘肃省卫生健康行业科研项目(GSWSKY2020-39)资助项目。

摘　　要：目的:对1例单纯型大疱性表皮松解症(EBS)患儿及其家系进行基因突变检测和致病性分析。方法:应用高通量二代测序技术捕获目标序列,对患儿进行全外显子组测序。发现致病位点后,应用Sanger测序法进行家系验证,查阅人类基因突变数据库(HGMD),运用生物信息学蛋白功能预测软件,分析变异位点的致病性。结果:患儿角蛋白5(KRT5)基因的第一外显子检出杂合变异c.536T>C(p.F179S),该变异造成KRT5蛋白的第179位氨基酸改变,患儿父母均未检测到相同突变。结论:患儿KRT5基因的杂合变异c.536T>C(p.F179S)为新发致病性变异,导致患儿KRT5缺陷,进而引发疱疹样型EBS(DM-EBS)。该变异位点在国内未见报道,扩大了我国人群KRT5的基因突变谱,为家系的遗传咨询和产前诊断提供依据。Objective:To identify mutations of the KRT5 gene and to analyze the pathogenicity of the KRT5 gene mutation in a child with epidermolysis bullosa simplex.Methods:A whole exome sequencing by high-throughput targeted exome sequencing was performed.The candidate variants were verified by using Sanger sequencing,the Human Gene Mutation Database(HGMD) was checked,and bioinformatics protein function prediction software was used to analyze the pathogenicity of mutation.Results:The heterozygous mutation c.536T>C(p.F179S) was detected in the first exon of the KRT5 gene of the patient.This mutation caused the amino acid change at 179 of the KRT5 protein.There was no mutation detected in the parents of the child.Conclusion:The heterozygous mutation c.536T>C(p.F179S) in the KRT5 gene is a de novo pathogenic variant,which leads to the defect of KRT5 protein and causes Dowling-Meara EBS.The finding of this variant expands the gene mutation spectrum of KRT5in the Chinese population and provides the basis for genetic counseling and prenatal diagnosis.

关 键 词：表皮松解症 大疱性 单纯型 角蛋白5 基因变异 

分 类 号：R758.59[医药卫生—皮肤病学与性病学]