Identification of a novel MYO7A mutation in Usher syndrome type 1
Identification of a novel MYO7A mutation in Usher syndrome type 1
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1 型 Usher 综合征中新型 MYO7A 突变的鉴定
DOI：
10.18632/oncotarget.23408
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Zhang, Li
中科院分区：
文献类型：
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作者：
Cheng, Ling;Yu, Hongsong;Zhang, Li
Usher综合征（USH）是一种以耳聋和视网膜色素变性为特征的常染色体隐性遗传病。鉴于USH的高表型和遗传异质性，用传统方法进行遗传筛查是不切实际的。在本研究中，我们进行了有针对性的下一代测序（NGS），以揭示USH家族（2例USH患者和15名未受影响的亲属）的潜在基因。选择了135个与遗传性视网膜变性相关的基因进行深度外显子组测序。随后，利用变异分析、桑格验证和分离检验来鉴定该家系中的致病突变。所有受影响的人都有一个典型的USH I型（USH 1）表型，其中包括耳聋，前庭功能障碍和视网膜色素变性。靶向NGS和桑格测序验证表明，USH1患者携带一个未报告的剪接位点突变，c.5168+1G>A，作为MYO7A基因中c.6070 C>T（p.R2024 X）的复合杂合突变。一项功能研究显示，携带杂合突变的个体中MYO7A基因表达降低。总之，靶向下一代测序为USH1提供了全面有效的诊断。这项研究揭示了MYO7A基因的遗传缺陷，并扩大了与USH1突变相关的临床表型谱。
Usher syndrome (USH) is an autosomal recessive disease characterized by deafness and retinitis pigmentosa. In view of the high phenotypic and genetic heterogeneity in USH, performing genetic screening with traditional methods is impractical. In the present study, we carried out targeted next-generation sequencing (NGS) to uncover the underlying gene in an USH family (2 USH patients and 15 unaffected relatives). One hundred and thirty-five genes associated with inherited retinal degeneration were selected for deep exome sequencing. Subsequently, variant analysis, Sanger validation and segregation tests were utilized to identify the disease-causing mutations in this family. All affected individuals had a classic USH type I (USH1) phenotype which included deafness, vestibular dysfunction and retinitis pigmentosa. Targeted NGS and Sanger sequencing validation suggested that USH1 patients carried an unreported splice site mutation, c.5168+1G>A, as a compound heterozygous mutation with c.6070C>T (p.R2024X) in the MYO7A gene. A functional study revealed decreased expression of the MYO7A gene in the individuals carrying heterozygous mutations. In conclusion, targeted next-generation sequencing provided a comprehensive and efficient diagnosis for USH1. This study revealed the genetic defects in the MYO7A gene and expanded the spectrum of clinical phenotypes associated with USH1 mutations.