Hearing loss associated with an unusual mutation combination in the gap junction beta 2 (GJB2) gene in a Chinese family

Abstract Objective To assess the molecular etiology of nonsyndromic sensorineural hearing loss (NSHL) in members of an affected Chinese family. Methods Common hearing-related genes including gap junction beta 2 ( GJB2 ), SLC26A4 , mitochondrial DNA 12S rRNA , GJB3 and GJB6 were examined in a family consisting of a normal hearing father, an NSHL-affected mother, one normal-hearing child and three NSHL-affected children. Specific primers were used in polymerase chain reactions to amplify the coding regions of the above genes from the peripheral blood DNA from each family member, and the genes were analyzed by direct sequencing. The subjects were evaluated for phenotypic characterization using audiometric testing and radiological examination of the inner ear. Results Pathogenic mutations in the GJB2 gene were identified. The affected mother showed a heterozygous G → A transition at nucleotide 232, resulting in an alanine to threonine substitution at codon 78 (p.A78T), and the normal hearing father had a c.35insG insertion mutation. The three affected children displayed heterozygosity for the GJB2 mutations, showing a previously unreported combination of c.35insG and c.232G>A. Conclusions The GJB2 mutations account for a significant proportion of NSHL in affected individuals worldwide. Genetic and audiological data analysis of a Chinese family with NSHL revealed a novel c.35insG/c.232G>A compound heterozygous state. Our results highlight the complexity of the GJB2 genotypes and phenotypes.