Abstract
BACKGROUND: Hereditary hearing loss is a heterogeneous class of disorders showing various patterns of inheritance and involving many genes. Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus. METHODS: We report on a Chinese family with sensorineural, progressive hearing loss. Next-generation sequencing (NGS) was conducted using DNA samples from this family. A candidate mutation was confirmed by Sanger sequencing. A detailed genotype and phenotype analysis of EYA4 in deafness is provided. RESULTS: NGS revealed an insertion mutation c.544_545insA in exon 8 of EYA4 in all affected family members. This insertion created a frameshift resulting in a stop codon at position 221 (p.F221X). The p.F221X frameshift mutation cosegregated with hearing loss in the family. Audiograms of affected family members are flat or sloping, differing from the characteristic "cookie bite" audiogram and the mutation is localized in a different region of the eyaHR in EYA4. CONCLUSIONS: We identified a novel frameshift mutation in the EYA4 gene. Our results enrich the mutational spectrum of EYA4 and highlight the complexity of the DFNA10 genotypes and phenotypes. Using NGS techniques to establish a database of common mutations in patients with hearing loss and further data accumulation will contribute to the early diagnosis and development of fundamental therapies for hereditary hearing loss.