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

梁宾;荣伽玲;张晓康;何思颖;向阳;罗晶;张元珍;马建鸿;杨国华;郑芳;

1:武汉大学中南医院检验科

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

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。
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
基金项目(Foundation):
湖北省卫健委创新团队项目(WJ2019C002)
作者
梁宾;荣伽玲;张晓康;何思颖;向阳;罗晶;张元珍;马建鸿;杨国华;郑芳;
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