一个表型差异较大的耳聋家系的基因诊断和遗传分析

Strategies for the analysis of a hearing loss family with large phenotypic differences

华澄宇;杨冰倩;华清泉

1:武汉大学人民医院耳鼻咽喉头颈外科

摘要
目的 鉴定一个成员表型差异较大的耳聋家系的致病基因并评估其听觉干预效果。方法 询问家系内成员病史及既往史,并对患者行全基因组检测筛选致病变异,通过Sanger测序验证。结果 该家系共三代13人,现存6人,4例耳聋患者(Ⅲ-1、Ⅲ-2、Ⅲ-4、Ⅲ-5)。先证者Ⅲ-1双耳极重度听力下降,进行性加重,进展较快,有多次骨折史,检出COL1A2 c577G>A(p.Gly193Ser)杂合突变,以及GJB2 c.109G>A(p.Val37Ile)纯合突变,双侧序贯人工耳蜗植入后效果满意;Ⅲ-5双耳混合性听力下降,亦有多次骨折史,检出COL1A2 c577G>A(p.Gly193Ser)杂合变异,佩戴助听器效果满意;这两例诊断为成骨不全。Ⅲ-2为右耳突发重度感音神经性聋,Ⅲ-4为左耳混合性听力下降,这两例未筛选到候选变异,疑为其他因素导致的听力损失。结论 基因测序检出了该家系COL1A2和GJB2两个致病基因,耳聋基因诊断应注意患者基因型和表型是否一致,必要时进行个体化分析。
关键词
耳聋;COL1A2;GJB2;个体化遗传分析
基金项目(Foundation):
武汉大学专业学位研究生教育综合改革项目(600460110)
作者
华澄宇;杨冰倩;华清泉
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华澄宇杨冰倩华清泉