Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China

Abstract

The myosin VIIA (MYO7A) gene encodes a protein classified as an unconventional myosin. Mutations within MYO7A can lead to both syndromic and non-syndromic hearing impairment in humans. Among different mutations reported in MYO7A, only five led to non-syndromic sensorineural deafness autosomal dominant type 11 (DFNA11). Here, we present the clinical, genetic and molecular characteristics of two large Chinese DFNA11 families with either high- or low-frequency hearing loss. Affected individuals of family DX-J033 have a sloping audiogram at young ages with high frequency are most affected. With increasing age, all test frequencies are affected. Affected members of family HB-S037 present with an ascending audiogram affecting low frequencies at young ages, and then all frequencies are involved with increasing age. Genome-wide linkage analysis mapped the disease loci within the DFNA11 interval in both families. DNA sequencing of MYO7A revealed two novel nucleotide variations, c.652G > A (p.D218N) and c.2011G > A (p.G671S), in the two families. It is for the first time that the mutations identified in MYO7A in the present study are being implicated in DFNA11 in a Chinese population. For the first time, we tested electrocochleography (ECochG) in a DFNA11 family with low-frequency hearing loss. We speculate that the low-frequency sensorineural hearing loss in this DFNA11 family was not associated with endolymphatic hydrops. © 2011 The Japan Society of Human Genetics All rights reserved.