DFNA20/26型耳聋致聋基因ACTG1突变及临床特征分析

DFNA20/26 hearing impairment:The mutation of the ACTG1 gene and its phenotypic analysis

目的分析两个渐进性耳聋家系的遗传学病因,探讨DFNA20/26型耳聋致聋基因突变和听力学表征。方法收集详细家族史信息,完善听力学等临床检查;抽取受试者外周静脉血,利用全外显子组测序鉴定致聋突变;检索DFNA20/26型耳聋既往文献,总结ACTG1基因突变和相应听力表型。结果2个家系共4例耳聋患者均表现语后渐进性非综合征型听力损失。基因检测发现家系1耳聋患者携带ACTG1基因c.721G>A杂合变异,家系2先证者携带c.773C>G变异;DFNA20/26型耳聋表现为语后渐进性听力损失,发病年龄主要集中在第1和第2个10年期,听力损失以初始累及高频为主的下降型曲线常见,并随年龄增加最终进展为全频的重度-极重度聋(约1 dB/年)。结论ACTG1:c.721G>A杂合变异为家系1耳聋患者致聋病因,家系2 ACTG1:c.773C>G为本文首次报道。DFNA20/26型耳聋突变谱和听力学表型的阐述可为后续遗传咨询提供参考。

Objective To provide an etiological diagnosis for two Chinese family with non-syndromic progressive hearing loss and discuss clinical audiological characteristics of the ACTG1 mutations that caused DFNA20/26 hearing impairment.Methods Information of family history was collected and genealogy was drawn.A comprehensive physical examination,audiological and radiological tests were performed in affected individuals.Peripheral blood from all subjects was obtained for DNA extraction,then whole-exome sequencing was applied to screen candidate variants.The literature was retrieved to summarize the audiological characteristics of DFNA20/26 hearing impairment.Results All patients presented with post-lingual progressive non-syndromic sensorineural hearing loss.Genetic testing identified two ACTG1 variants in family 1 and family 2:c.721G>A and c.773C>G,respectively.ACTG1 mutations cause DFNA20/26 hearing impairment beginning in the one to two decades which was initially predominated at high frequencies and later deteriorated to severe to profound HL at full frequencies with age(-1 dB/year).Conclusions The etiology of hearing loss in family 1 was attributed to c.721G>A mutation.The findings of c.773C>G mutation supplement the mutation spectrum of the ACTG1 gene,and the elucidation of phenotypic features is beneficial to enhance clinicians'knowledge of DFNA20/26 hearing impairment and facilitate genetic counseling for the family.