DDOD综合征ATP6V1B2基因新发变异及遗传学分析  

Genetic Analysis of New Variation of ATP6V1B2 Gene in DDOD Syndrome

作　　者：梁宾 荣伽玲 张晓康 何思颖 向阳 罗晶[1] 张元珍[2] 马建鸿[2,3] 杨国华 郑芳[1,3] Liang Bin;Rong Jialing;Zhang Xiaokang;He Siying;Xiang Yang;Luo Jing;Zhang Yuanzhen;Ma Jianhong;Yang Guohua;Zheng Fang(Zhongnan Hospital of Wuhan University,Wuhan,430071,China;不详)

机构地区：[1]武汉大学中南医院检验科,武汉430071 [2]武汉大学中南医院妇产科 [3]湖北省产前诊断与优生临床医学研究中心 [4]武汉大学基础医学院遗传学教研室

出　　处：《听力学及言语疾病杂志》2020年第4期363-367,共5页Journal of Audiology and Speech Pathology

基　　金：湖北省卫健委创新团队项目(WJ2019C002)。

摘　　要：目的对一例DDOD综合征先证者进行基因突变检测和遗传学分析,探讨ATP6V1B2致病基因突变与先证者临床特征的联系,为该家系的遗传咨询提供依据。方法收集一例先天性感音神经性聋伴指骨、牙齿发育异常的先证者(女,6岁)及其父母的临床资料,提取先证者及父母的外周全血基因组DNA,采用二代测序(next-generation sequencing,NGS)法筛查先证者的潜在致病基因位点,用Sanger测序法对变异位点进行验证,用遗传学数据库资料和生物信息学分析软件对变异位点进行分析。结果二代测序和Sanger测序结果共同显示先证者存在ATP6V1B2 c.1517G>A (p.R506Q)杂合突变,其父母表型均正常且未检出相应的异常突变;遗传学数据资料和相关文献检索显示ATP6V1B2 c.1517G>A (p.R506Q)为新发突变;生物信息学软件分析显示,ATP6V1B2 c.1517G>A突变会对蛋白质的二级结构和理化性质产生一定影响,从而导致DDOD综合征者指骨和牙齿发育不全等表型异常。结论先证者ATP6V1B2 c.1517G>A (p.R506Q)为新发的致病性突变,该突变可能导致先天性聋伴甲发育不全综合征的发生。Objective Gene mutation detection and genetic analysis were carried out on a patient with deafness and onycho-osteodystrophy to explore the relationship between ATP6 V1 B2 pathogenic gene mutation and clinical phenotype, so as to provide evidence for genetic counseling and prenatal diagnosis. Methods We collected clinical data of the proband and her family members. With genomic DNA extracted from peripheral blood, potential mutation sites were detected by next-generation sequencing(NGS), potential mutation sites were validated by Sanger sequencing. Genetic database data and bioinformatics analysis software were used to evaluate the pathogenicity of mutation sites. Results The sequencing results revealed a missense c.1517 G>A(p.R506 Q) variant in the exon 14 of ATP6 V1 B2 gene of the proband but not her parents, which was unreported previously. Bioinformatics analysis suggested that the variant would affect the secondary structure and physicochemical properties of the protein. Conclusion ATP6 V1 B2 c.1517 G>A(p.R506 Q) is a novel de novo missense variant in the proband, which may lead to the occurrence of DDOD syndrome.

关 键 词：ATP6V1B2基因 基因突变 DDOD综合征 二代测序 生物信息学分析 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]