Mutation in the zonadhesin-like domain of alpha-tectorin associated with autosomal dominant non-syndromic hearing loss

A gene responsible for autosomal dominant non-syndromic hearing impairment in two families (DFNA8 and DFNA12) has recently been identified as TECTA en coding alpha-tectorin, a major component of the tectorial membrane. In thes e families, missense mutations within the zona pellucida domain of alpha-te ctorin were associated with stable severe mid-frequency hearing loss, The p resent study reports linkage to DFNA12 in a new family with autosomal domin ant high frequency hearing loss progressing from mild to moderate severity. The candidate region refined to 3.8 cM still contained the TECTA gene, A m issense mutation (C1619S) was identified in the zonadhesin-like domain, Thi s mutation abolishes the first of the vicinal cysteines ((1619)Cys-Gly-Leu- (1622)Cys) present in the D4 von Willebrand factor (vWf) type D repeat. The se results further support the involvement of TECTA mutations in autosomal dominant hearing impairment, and suggest that vicinal cysteines are involve d in tectorial membrane matrix assembly.