title: 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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Hanjun
authors.initials: H
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Jin
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ouyang
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Weiyan
authors.initials: W
authors.lastname: Yang
authors.forename: Rongguang
authors.initials: R
authors.lastname: Wang
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002681:China; D005190:Family; D005260:Female; D008040:Genetic Linkage; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins