一个常染色体显性遗传性聋家系的临床表型及致病变异分析

Clinical phenotype and pathogenic variation analysis of an autosomal dominant deafness family

蔡梦菲;张婷;何万里;张梦丽;张晓赛;许红恩;陈蓓

1:郑州大学第一附属医院耳科

2:郑州大学医学科学院

3:天健先进生物医学实验室

摘要
目的 研究一个常染色体显性遗传非综合征型聋的家系,以明确其临床表型及可能的分子遗传学病因。方法 详细询问先证者(Ⅳ-8)病史及家族史,进行体格检查及听力学、颞骨CT等检查。提取先证者(Ⅳ-8)的外周血基因组DNA进行全外显子组测序,对候选变异在家系成员中进行Sanger测序验证。结果 该家系共4代36人,为常染色体显性遗传,其中16人表现为进行性听力下降,对其中13人进行听力学检查,3人(Ⅲ-1、Ⅲ-11、Ⅳ-4)听力正常,余10人(Ⅱ-2、Ⅱ-4、Ⅱ-10、Ⅲ-4、Ⅲ-10、Ⅲ-13、Ⅲ-14、Ⅳ-1、Ⅳ-7、Ⅳ-8)表现为不同程度的双耳对称性听力损失,听力下降程度与年龄相关。先证者(Ⅳ-8)全外显子组测序发现其携带NM_199330.2(HOMER2):c.1064 A>G (p.Ter354Trpext*10)变异,Sanger测序验证了该位点的变异。共采集到该家系18人的外周血液样本,除一名成员(Ⅳ-6)携带该变异年龄较小尚未表现出听力下降外,家系中听力下降患者(Ⅱ-2、Ⅱ-4、Ⅱ-10、Ⅲ-4、Ⅲ-9、Ⅲ-10、Ⅲ-13、Ⅲ-14、Ⅳ-1、Ⅳ-7、Ⅳ-8)均携带HOMER2基因c.1064 A>G (p.Ter354Trpext*10)杂合变异;听力正常的个体(Ⅱ-5、Ⅲ-1、Ⅲ-5、Ⅲ-11、Ⅳ-2、Ⅳ-4)均未携带该变异,听力表型与基因型共分离。该变异评级为可能致病(PM2+PP1+PM4)。结论 HOMER2基因c.1064 A>G (p.Ter354Trpext*10)为该遗传性聋家系的分子遗传学病因。
关键词
HOMER2基因;常染色体显性遗传性非综合征型感音神经性聋68型(DFNA68);终止密码子变异
基金项目(Foundation):
河南省医学科技攻关省部共建重点项目(SBGJ202102163)
作者
蔡梦菲;张婷;何万里;张梦丽;张晓赛;许红恩;陈蓓
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