title: Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal Dominant Non-Syndromic Hearing Loss.
abstract: Autosomal dominant non-syndromic hearing loss is highly heterogeneous, and eyes absent 4 (EYA4) is a disease-causing gene. Most EYA4 mutations founded in the Eya-homologous region, however, no deafness causative missense mutation in variable region of EYA4 have previously been found. In this study, we identified a pathogenic missense mutation located in the variable region of the EYA4 gene for the first time in a four-generation Chinese family with 57 members. Whole-exome sequencing (WES) was performed on samples from one unaffected and two affected individuals to systematically search for deafness susceptibility genes, and the candidate mutations and the co-segregation of the phenotype were verified by polymerase chain reaction amplification and by Sanger sequencing in all of the family members. Then, we identified a novel EYA4 mutation in exon 8, c.511G>C; p.G171R, which segregated with postlingual and progressive autosomal dominant sensorineural hearing loss (SNHL). This report is the first to describe a missense mutation in the variable region domain of the EYA4 gene, which is not highly conserved in many species, indicating that the potential unconserved role of 171G>R in human EYA4 function is extremely important.
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Jiongjiong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institutes of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xia
authors.affiliation: Institutes of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Hao
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China; Institutes of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Zhaoxin
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001299:Audiometry; D059472:Exome; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*
chemical_list: C117736:EYA4 protein, human; D015534:Trans-Activators