A novel mutation of EYA4 in a large Chinese family with autosomal dominant middle-frequency sensorineural hearing loss by targeted exome sequencing

The middle-frequency sensorineural hearing loss (mfsnhl) is rare among hereditary non-syndromic hearing loss. to date, only three genes are reported to be associated with mfsnhl, including tecta, eya4 and col11a2. in this report, we analyzed and explored the clinical audiological characteristics and the causative gene of a chinese family named hg-z087 with non-syndromic autosomal dominant inherited mfsnhl. clinical audiological characteristics and inheritance pattern of a family were evaluated, and pedigree was drawn based on medical history investigation. our results showed that the chinese family was characterized by late onset, progressive, non-sydromic autosomal dominant mfsnhl. targeted exome sequencing, conducted using dna samples of an affected member in this family, revealed a novel heterozygous missense mutation c.1643c>g in exon 18 of eya4, causing amino-acid (aa) substitution arg for thr at a conserved position aa-548. the p.t548r mutation related to hearing loss in the selected chinese family was validated by sanger sequencing. however, the mutation was absent in control group containing 100 dna samples from normal chinese families. in conclusion, we identified the pathogenic gene and found that the novel missense mutation c.1643c>g (p.t548r) in eya4 might have caused autosomal dominant non-syndromic hearing impairment in the selected chinese family.