title: A novel compound heterozygous mutation in the GJB2 gene causing non-syndromic hearing loss in a family.
abstract: Mutations in the GJB2 gene are responsible for up to 50% of cases of non-syndromic recessive hearing loss, with c.35delG, c.167delT and c.235delC being the predominant mutations in many world populations. However, a large number of rare mutations in this gene may also contribute to hearing loss. The aim of the present study was to conduct a clinical and molecular characterization of a Chinese family with non-syndromic hearing loss. Sequence analysis of the GJB2 gene led to the identification of a novel compound heterozygous mutation c.257C>G (p.T86R)/c.605ins46 in two profoundly deaf siblings whose hearing parents were each heterozygous, either for the c.257C>G (paternal) or for the c.605ins46 (maternal) mutations. Both c.257C>G and c.605ins46 are rare GJB2 mutations that have previously been reported to segregate with autosomal recessive hearing loss exclusively in East Asian populations. To study the pathogenic effect of the compound heterozygous mutation, a three-dimensional model was constructed and Anolea mean force potential energy was predicted for a bioinformatic structural analysis. HEK293 cells were used to study the pathogenic effect of mutant connexin 26 proteins. The results suggested that the c.257C>G (p.T86R)/c.605ins46 mutations in the GJB2 gene provides a novel molecular explanation for the role of the GJB2 gene in hearing loss.
authors: Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Qinjun
authors: Q
authors: Wei
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Youguo
authors: Y
authors: Liu
authors: Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Shuai
authors: S
authors: Wang
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Tingting
authors: T
authors: Liu
authors: Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Yajie
authors: Y
authors: Lu
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Guangqian
authors: G
authors: Xing
authors: Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors: Xin
authors: X
authors: Cao
mesh_terms: D044466:Asian People / Q000235:genetics*; D003001:Cloning, Molecular; D019295:Computational Biology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26