title: A novel dominant GJB2 (DFNA3) mutation in a Chinese family.
abstract: To decipher the phenotype and genotype of a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) and a novel dominant missense mutation in the GJB2 gene (DFNA3), mutation screening of GJB2 was performed on the propositus from a five-generation ADNSHL family through polymerase chain reaction amplification and Sanger sequencing. The candidate variation and the co-segregation of the phenotype were verified in all ascertained family members. Targeted genes capture and next-generation sequencing (NGS) were performed to explore additional genetic variations. We identified the novel GJB2 mutation c.524C > A (p.P175H), which segregated with high frequency and was involved in progressive sensorineural hearing loss. One subject with an additional c.235delC mutation showed a more severe phenotype than did the other members with single GJB2 dominant variations. Four patients diagnosed with noise-induced hearing loss did not carry this mutation. No other pathogenic variations or modifier genes were identified by NGS. In conclusion, a novel missense mutation in GJB2 (DFNA3), affecting the second extracellular domain of the protein, was identified in a family with ADNSHL.
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Wu
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Linyi
authors.initials: L
authors.lastname: Xie
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.affiliation: Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Wang
mesh_terms: D044466:Asian People; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005192:Family Health; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26