Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive non-syndromic

• 作 者: 胡炯炯;
• 机 构: 上海市东方医院耳鼻咽喉科
• 出 处: 第十四次全国医学遗传学学术会议
• 发表日期: 2015年期

　　Background: Autosomal recessive non-syndromic hearing loss (ARNSHL) is highly heterogeneous, and transmembrane channel-like 1 gene is a disease-causing gene.So far, 35 homozygous mutations in TMC1 were shown to be associated with ARNSHL found in over 60 families worldwide.However, only one of those mutations was detected in Chinese populations.Methods: In this study, we discovered a pathogenic missense mutation located in the T5-T6 domain of the TMC1 gene in a three-generation Chinese family with 14 members.Whole Exome Sequencing was performed on samples from one unaffected and two affected individuals to systematically search for deafness susceptibility genes, and the candidate mutations and the co-segregation of the phenotype were verified by polymerase chain reaction amplification and by Sanger sequencing in all of the family members.Results: Then, we identified a novel TMC1 mutation in exon 20,c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss.Conclusions: This report describe a new missense mutation in the T5-T6 domain of the TMC1 gene, which is highly conserved in many species, indicating that the potential conserved role of p.P660L in human TMC1 function is extremely important.