Identification of a novel mutation of EYA4 in a Chinese family with delayed nonsyndromic hearing loss and analysis of molecular epidemiology of EYA4 mutations

Background : EYA4 is responsible for DFNA10 deafness. Because of its insidious onset and slow progression, hearing loss in ADSHL is usually difficult to detect early in clinical settings and the intervention is relatively backward. Genetic testing can help to detect hearing loss early and facilitate early intervention, effectively reducing the disability rate and improving the quality of life of patients. Methods: In this study, we report a Chinese family with delayed onset and progressive hearing loss that passed down for four generations. The whole-exome sequencing (WES) was performed on DNA samples from the proband. Candidate variants in the proband and his family members were confirmed by Sanger sequencing. In silico prediction tools and co-segregation analyses were used to determine the pathogenicity of identified variants. A literature review of known EYA4 mutations was performed, and the mutation frequency, distribution characteristics in different populations, and correlation between genotypes and phenotypes were analyzed. Results: We identified a novel EYA4 gene mutation, c.1745_1748del (p.Glu582ValfsTer6), in a Chinese family with nonsyndromic ADNSHL. This mutation was predicted to result in a frameshift and a stop codon after six additional amino acids and confirmed co-segregation with the phenotype of this family. To date, 52 pathogenic mutations in EYA4 have been reported, and most of these mutations have been identified in Asian populations: 15 mutations in Japan, 10 in China, and four in Korea. In addition, the EYA4 mutation is not a common pathogenic gene of ADNSHL, and its audiological features are highly heterogeneous. Conclusions: A novel mutation in EYA4 was identified in a Chinese family with delayed-onset deafness, further enriching the mutation spectrum of EYA4 . The audiological features of EYA4 mutations are highly heterogeneous and usually difficult to detect early in clinical settings. Our findings highlight the importance of genetic testing in patients with late-onset hearing loss.