USH2A新复合杂合突变引起中度感音神经性耳聋

Identification of Novel Compound Heterozygous Mutations of Deafness Gene USH2A Related to Autosomal Recessive Nonsyndromic Hearing Loss

目的寻找并确定一例中度感音神经性耳聋患者的遗传分子病因，探讨该突变的致病性，为该家庭再生育提供遗传指导。方法采集一个耳聋小家系（No．1501ZJS）样本3例，包括1例听力下降患者、2例正常听力父母亲，临床资料完整；对No．1501ZJS家系患者样本进行140个已知耳聋基因捕获、二代测序及生物信息学分析，确定可疑致病突变后采用突变位点PCR扩增，Sanger测序在该家系内部进行验证。采用生物信息学方法对新突变的致病性进行预测。结果USH2A基因复合杂合突变c．8342C〉T（p．T2781I）和c．6628C〉G（p．P2210A）是No．1501ZJS家系的致聋突变。结论目标区域捕获结合二代测序技术为具有高度遗传异质性的耳聋个体及家庭提供了有力的检测手段。采用该方法我们成功为No．1501ZJS家庭明确了致聋突变，其中c．8342C〉T（p．T2781I）是已报道的致聋突变，而c．6628C〉G（p．P2210A）则为首次发现。我们的研究丰富了遗传性聋的突变谱。

Objective To identify causative mutations of autosomal recessive nonsyndromic hearing loss （ARNSHL） in a nonconsanguineous family （No.1501ZJS）, and provide the basic information for the molecular diagnosis of genetic hearing loss. Methods The blood samples and clinical data of family No.1501ZJS were collected, including patients and parents with normal hearing.The140 known deafness genes were targeted and next generation sequencing and bioinformatic analysis were carried out in the patients to determine the suspected causative mutation. The PCR amplification of the mutation site and Sanger sequencing were carried out to validate in the family.To identify the pathogenicity of novel mutation, bioinformatic analysis was carried out. Results Two compound heterozygous, disease-segregating mutations c.8342C〉T （p.T2781I）and c.6628C〉G （p.P2210A）were identified in USH2A genes. Conclusion The Target region capture technology combined with nextgeneration sequencing provides a powerful tool for the detection of deaf individuals and families with a high degree of genetic heterogeneity.By this means, we identifythat the hearing loss in the family No.1501ZJS is caused by novel compound heterozygous mutationsc.8342C〉T （p.T2781I） and c.6628C〉G （p.P2210A）in USH2A, the former is known and the latter is found for the first time, which enriched genetic hearing loss mutation spectrum.