title: A novel recessive truncating mutation in MYO15A causing prelingual sensorineural hearing loss.
abstract: Hearing loss (HL) is one of the most common human defects which affects millions of people globally. The identification of deafness-related genes or loci may facilitate basic and clinical translational research on this disorder. Here, we investigated a Chinese family with autosomal recessive non-syndromic hearing impairment. Using targeted massively parallel sequencing, we identified a novel homozygous mutation, c.3525_3526insA and p.Q1175fsX1188 (NM_016239), in exon 2 of MYO15A. Sanger sequencing confirmed that affected siblings were homozygous for the mutation, whereas both normal hearing parents were heterozygous. The mutation was absent in 96 healthy controls and public databases. The insertion leads to a frameshift and a truncated form of the protein, resulting in the pathogenic effect of hearing loss for the patients. Mutations in exon 2 of MYO15A may cause a less severe phenotype, facilitating the rapid identification of mutations in exon 2 among the 66 exons when linkage of less severe hearing loss to Deafness, Autosomal Recessive 3 (DFNB3) is detected. Our data provide additional molecular information for establishing a better genotype-phenotype understanding of DFNB3.
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Hearing Medicine Key Laboratory of Ministry of Health, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Research Center, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Hearing Medicine Key Laboratory of Ministry of Health, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Hearing Medicine Key Laboratory of Ministry of Health, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Qianru
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Hearing Medicine Key Laboratory of Ministry of Health, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Hearing Medicine Key Laboratory of Ministry of Health, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China; Hearing Medicine Key Laboratory of Ministry of Health, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China. Electronic address: cfdai66@163.com.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Dai
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: C485245:MYO15A protein, human; D009218:Myosins
keywords: Exon 2; Hearing loss; MYO15A