TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss
TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss
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DOI：
10.1007/s00405-015-3671-0
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发表时间：
2016-05-01
影响因子：
2.6
通讯作者：
Podkrajsek, Katarina Trebusak
中科院分区：
文献类型：
--
作者：
Battelino, Saba;Klancar, Gasper;Podkrajsek, Katarina Trebusak
非综合征性遗传性耳聋在临床表现、遗传方式和潜在遗传原因方面具有高度异质性。编码跨膜丝氨酸蛋白酶的TMPRSS3基因突变占高加索人常染色体隐性遗传性非综合征性听力损失（ARNSHL）的<1%。在一个有极重度耳聋父母和一个儿子的索引家族中采用靶向下一代测序，并在35名疑似ARNSHL患者的队列中采用选定的TMPRSS 3基因区域的桑格测序。该家系中的一个儿子和他的母亲是TMPRSS 3 c.208delC（p.His70Thrfs*19）变体的纯合型。父亲是同一变异体和共同GJB 2 c.35delG变异体的双基因复合杂合子。来自ARNSHL队列的另外三名患者是TMPRSS 3 c.208delC纯合型。TMPRSS3缺陷似乎是斯洛文尼亚ARNSHL的一个重要原因，导致严重先天性听力损失的统一表型，以及人工耳蜗植入后令人满意的听力和语言识别结果。因此，TMPRSS3基因分析应与GJB 2和GJB 6基因一起沿着在ARNSHL遗传学研究的第一层。
Nonsyndromic genetic deafness is highly heterogeneous in its clinical presentation, pattern of inheritance and underlying genetic causes. Mutations in TMPRSS3 gene encoding transmembrane serine protease account for < 1 % of autosomal recessive nonsyndromic hearing loss (ARNSHL) in Caucasians. Targeted next generation sequencing in the index family with profound deaf parents and a son, and Sanger sequencing of selected TMPRSS3 gene regions in a cohort of thirty-five patients with suspected ARNSHL was adopted. A son and his mother in the index family were homozygous for TMPRSS3 c.208delC (p.His70Thrfs*19) variant. Father was digenic compound heterozygote for the same variant and common GJB2 c.35delG variant. Three additional patients from the ARNSHL cohort were homozygous for TMPRSS3 c.208delC. TMPRSS3 defects seem to be an important cause of ARNSHL in Slovenia resulting in uniform phenotype with profound congenital hearing loss, and satisfactory hearing and speech recognition outcome after cochlear implantation. Consequently, TMPRSS3 gene analysis should be included in the first tier of genetic investigations of ARNSHL along with GJB2 and GJB6 genes.