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首页> 外文期刊>Human mutation >A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.
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A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.

机译：对患有非综合征性听力障碍和听觉神经病的受试者中的otoferlin基因（OTOF）突变的发生率和范围进行的多中心研究。

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摘要

Autosomal recessive nonsyndromic hearing impairment (NSHI) is a heterogeneous condition, for which 53 genetic loci have been reported, and 29 genes have been identified to date. One of these, OTOF, encodes otoferlin, a membrane-anchored calcium-binding protein that plays a role in the exocytosis of synaptic vesicles at the auditory inner hair cell ribbon synapse. We have investigated the prevalence and spectrum of deafness-causing mutations in the OTOF gene. Cohorts of 708 Spanish, 83 Colombian, and 30 Argentinean unrelated subjects with autosomal recessive NSHI were screened for the common p.Gln829X mutation. In compound heterozygotes, the second mutant allele was identified by DNA sequencing. In total, 23 Spanish, two Colombian and two Argentinean subjects were shown to carry two mutant alleles of OTOF. Of these, one Colombian and 13 Spanish subjects presented with auditory neuropathy. In addition, a cohort of 20 unrelated subjects with a diagnosis of auditory neuropathy, from several countries, was screened for mutations in OTOF by DNA sequencing. A total of 11 of these subjects were shown to carry two mutant alleles of OTOF. In total, 18 pathogenic and four neutral novel alleles of the OTOF gene were identified. Haplotype analysis for markers close to OTOF suggests a common founder for the novel c.2905_2923delinsCTCCGAGCGCA mutation, frequently found in Argentina. Our results confirm that mutation of the OTOF gene correlates with a phenotype of prelingual, profound NSHI, and indicate that OTOF mutations are a major cause of inherited auditory neuropathy.
机译：常染色体隐性非综合征性听觉障碍（NSHI）是一种异质性疾病，目前已报告了53个遗传基因座和29个基因。其中之一OTOF编码otoferlin，一种膜锚定的钙结合蛋白，在听觉内部毛细胞带状突触的突触小泡的胞吐作用中发挥作用。我们已经研究了OTOF基因中失聪突变的患病率和频谱。筛选了708名西班牙人，83名哥伦比亚人和30名与阿根廷无关的常染色体隐性遗传性NSHI受试者，以寻找常见的p.Gln829X突变。在复合杂合子中，第二突变等位基因通过DNA测序鉴定。总共显示23名西班牙人，两名哥伦比亚人和两名阿根廷人携带两个OTOF突变等位基因。其中，一名哥伦比亚和13名西班牙受试者表现出听觉神经病。此外，通过DNA测序筛选了来自20多个国家的20个不相关受试者的队列，这些受试者被诊断出听觉神经病。这些受试者中总共有11名显示携带OTOF的两个突变等位基因。总共鉴定出OTOF基因的18个病原和4个中性新等位基因。对接近OTOF的标记的单倍型分析表明，这种新的c.2905_2923delinsCTCCGAGCGCA突变的共同创始人，该突变经常在阿根廷发现。我们的结果证实OTOF基因的突变与舌前深NSHI的表型相关，并表明OTOF突变是遗传性听觉神经病的主要原因。

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