A novel compound heterozygous mutation in the MYO15A gene in autosomal recessive hearing loss identified by targeted massively parallel sequencing

Objectives: Inherited genetic defects are the most common causes of autosomal recessive nonsyndromic hearing loss (ARNSHL), affecting millions of people worldwide. Identification and specific molecular diagnosis of the pathogenic genes or loci would facilitate basic research of ARNSHL and its clinical prevention and treatment. Materials and methods: We identified the causal deafness gene of a Chinese family with ARNSHL using targeted massively parallel sequencing. We also used DNA from 51 Chinese familial patients with ARNSHL and 60 ethnicity-matched normal controls to perform extended variants analysis. Results: We detected a novel compound heterozygous mutation, c. 10419_10423delCAGCT and a previously reported mutation c. 6956+9C>G, in MYO15A gene in the proband. Both mutations co-segregated with hearing loss in the Chinese family in our study and were absent in the 51 index patients and 60 ethnicity-matched normal controls. Conclusion: We identified a novel c. 10419_10423delCAGCT frameshift mutation, which results in a truncated MYO15A protein that lacks part of the second FERM domain and PDZ-ligand at the C terminus. Our results demonstrate that the novel c. 10419_10423delCAGCT mutation, in compound heterozygosity with the previously reported c. 6956+9C>G splicing site mutation, is the underlying cause of ARNSHL in this Chinese family. Our study extends the mutation spectrum of the MYO15A gene for establishing a better understanding of DFNB3. *Correspondence to: Xia Gao, Department of Otorhinolaryngology-Head and Neck Surgery, Drum Tower Hospital affiliated with Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), No. 321 Zhongshan Road, Nanjing, 210008, China, Tel: (+86)-13951829819; E-mail: gaoxiadth@outlook.com