Novel Mutations and Mutation Combinations of Cause Various Phenotypes in One Chinese Family with Autosomal Recessive Hearing Impairment.

Autosomal recessive hearing impairment with postlingual onset is rare. Exceptions are caused by mutations in the gene, which can lead to prelingual (DFNB10) as well as postlingual deafness (DFNB8). mutations can be classified as mild or severe, and the phenotype is dependent on the combination of mutations. The combination of two severe mutations leads to profound hearing impairment with a prelingual onset, whereas severe mutations in combination with milder mutations lead to a milder phenotype with postlingual onset. We characterized a Chinese family (number FH1523) with not only prelingual but also postlingual hearing impairment. Three mutations in , one novel mutation c.36delC [p.(Phe13Serfs⁎12)], and two previously reported pathogenic mutations, c.916G>A (p.Ala306Thr) and c.316C>T (p.Arg106Cys), were identified. Compound heterozygous mutations of p.(Phe13Serfs⁎12) and p.Ala306Thr manifest as prelingual, profound hearing impairment in the patient (IV: 1), whereas the combination of p.Arg106Cys and p.Ala306Thr manifests as postlingual, milder hearing impairment in the patient (II: 2, II: 3, II: 5), suggesting that p.Arg106Cys mutation has a milder effect than p.(Phe13Serfs⁎12). We concluded that different combinations of mutations led to different hearing impairment phenotypes (DFNB8/DFNB10) in this family.