COL4A5基因新变异导致遗传性血尿肾病耳聋综合征一家系  

Identification of a novel variant of COL4A5 gene in a pedigree affected with Alport syndrome

作　　者：刘晓伟 高明[1] 邹洋[1] 王丽娟[1] 康冉冉 徐佩文[1] 牛玉萍[1] 黄色新[1] 李杰[1] 解洪强 高媛[1] Liu Xiaowei;Gao Ming;Zou Yang;Wang Lijuan;Kang Ranran;Xu Peiwen;Niu Yuping;Huang Sexin;Li Jie;Xie Hongqiang;Gao Yuan(Center for Reproductive Medicine,National Research Center for Assisted Reproductive Technology and Reproductive Genetics,Key Laboratory for Reproductive Endocrinology of the Ministry of Education,Shandong University,Jinan,Shandong 250001,China)

机构地区：[1]山东大学生殖医学研究中心,国家辅助生殖与优生工程技术研究中心,生殖内分泌教育部重点实验室,济南250001

出　　处：《中华医学遗传学杂志》2020年第8期807-810,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1004900,2018YFC1003100);山东省重点研发计划(2017G006035);山东省自然科学基金(ZR2018PH006,ZR2018MC014)。

摘　　要：目的:探讨1个遗传性血尿肾病耳聋综合征(Alport综合征)家系的致病原因。方法:应用高通量测序和Sanger测序法检测先证者COL4A5基因的变异,并在家系其他成员及100名正常对照中进行Sanger测序验证。结果:测序结果显示该家系中的4例女性患者COL4A5基因均存在c.3293G>T(p.Gly1098Val)的杂合变异,2例男性患者为COL4A5基因c.3293G>T(p.Gly1098Val)变异半合子,而正常家系成员以及100名正常对照中均未检测到此变异。按照美国医学遗传学与基因组学学会遗传变异分类标准与指南,COL4A5基因c.3293G>T变异位点判读为致病性变异(PM1+PM2+PP1-S+PP3+PP4)。结论:COL4A5基因的c.3293G>T(p.Gly1098Val)变异会导致Gly-X-Y三联结构发生变化,可能是该家系的发病原因,新变异的检出丰富了COL4A5基因的变异谱。Objective To explore the genetic basis for a pedigree affected with Alport syndrome.Methods Next generation sequencing and Sanger sequencing was carried out to detect potential variant of the COL4A5 gene among members from the pedigree and 100 unrelated healthy controls.Results A novel missense c.3293G>T(p.Gly1098Val)variant was found in the COL4A5 gene among 6 affected members but not the unaffected members of the pedigree or the 100 healthy controls.According to the American College of Medical Genetics and Genomics standards and guidelines,the c.3293G>T variant was classified as pathogenic(PP1-strong+PM1+PM2+PP3+PP4).Conclusion By destructing the Gly-X-Y structure of its protein product,the c.3293G>T variant of the COL4A5 gene probably underlies the Alport syndrome in this pedigree.Above finding has enriched the spectrum of COL4A5 variants.

关 键 词：ALPORT综合征 COL4A5基因 DNA测序 基因变异 

分 类 号：R692[医药卫生—泌尿科学] R764.43[医药卫生—外科学]