Phenotype–Genotype Correlation in 295 Chinese Deaf Subjects with Biallelic Causative Mutations in the GJB2 Gene

The connexin 26 coding gene (GJB2) is the primary causative gene for nonsyndromic sensorineural hearing impairment (NSSHI). More than 100 mutations in this gene have been reported to be linked to hearing impairment (HI), from mild to profound hearing loss. To precisely estimate the impact of GJB2 mutations in the Chinese population, a cross-sectional study was performed to analyze the auditory data of Chinese patients with NSSHI.Two hundred ninety-five unrelated patients with NSSHI with biallelic mutations in GJB2 were recruited from seven provinces in Northern China from 2004 to 2008. The levels of HI and average pure tone audiometry were compared across different genotypes by χ(2) testing. The subjects with the genotypes of combined truncating mutations had more cases of severe HI than the subjects with a genotype of several nontruncating mutations. It was also revealed that subjects carrying either c.[79GA; 341AG]+[79GA; 341AG] or c.[109GA]+[79GA; 341AG] had significantly fewer cases of severe HI than the reference group of homozygous c.235delC, whereas the subjects carrying c.[235delC]+[176_191del16] had more cases of severe HI than the homozygous c.235delC group.This is the first study to clarify the correlations between different GJB2 biallelic genotypes and NSSHI phenotype in the Chinese population. The Chinese subjects with two truncating mutations in GJB2 were shown to correlate with more severe HI.