title: Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss.
abstract: Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder, generally manifested with prelingual hearing loss and absence of other clinical manifestations. The aim of this study is to identify the pathogenic gene in a four-generation consanguineous Chinese family with ARNSHL. A novel homozygous variant, c.9316dupC (p.H3106Pfs*2), in the myoxin XVa gene (MYO15A) was identified by exome sequencing and Sanger sequencing. The homozygous MYO15A c.9316dupC variant co-segregated with the phenotypes in the ARNSHL family and was absent in two hundred normal controls. The variant was predicted to interfere with the formation of the Myosin XVa-whirlin-Eps8 complex at the tip of stereocilia, which is indispensable for stereocilia elongation. Our data suggest that the homozygous MYO15A c.9316dupC variant might be the pathogenic mutation, and exome sequencing is a powerful molecular diagnostic strategy for ARNSHL, an extremely heterogeneous disorder. Our findings extend the mutation spectrum of the MYO15A gene and have important implications for genetic counseling for the family.
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China; Department of Emergency, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Hong
authors: H
authors: Xia
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Xiangjun
authors: X
authors: Huang
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China; Department of Medical Information, Xiangya School of Medicine, Central South University, Changsha, China.
authors: Yi
authors: Y
authors: Guo
authors: Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Pengzhi
authors: P
authors: Hu
authors: Department of Otolaryngology-Head Neck Surgery, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Guangxiang
authors: G
authors: He
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Xiong
authors: X
authors: Deng
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Hongbo
authors: H
authors: Xu
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Zhijian
authors: Z
authors: Yang
authors: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors: Hao
authors: H
authors: Deng
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003638:Deafness / Q000235:genetics / Q000473:pathology; D059472:Exome / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009218:Myosins / Q000235:genetics*; D010375:Pedigree
chemical_list: C485245:MYO15A protein, human; D009218:Myosins