Update of the spectrum of GJB2 mutations in 107 patients with nonsyndromic hearing loss in the Fujian population of China.

Mutations in the GJB2 gene, encoding connexin26, which is expressed in the inner ear, have been shown to be responsible for the majority of nonsyndromic hearing loss (NSHL) cases. To update and evaluate the spectrum and prevalence of GJB2 mutations in the Fujian population, we screened exon 2 (coding), exon 1, and flanking introns of GJB2 in 107 NSHL probands and 61 individuals with normal hearing. Twelve different variants were identified, including three pathogenic mutations (c.235delC, c.299_300delAT, and c.508insAACG), one hypomorphic allele (p.V37I), three polymorphic variants (p.V27I, p.E114G, and p.I230T), and five rare variants (p.N62N, p.F115C, p.T123N, p.G21E, and p.F142I). The p.G21E and p.F142I variants were potentially pathogenic as predicted by PolyPhen-2, SIFT, and PROVEAN. The most common mutation was c.235delC with allele frequency 12.6% (27/214). The most common polymorphisms in the Fujian population were p.V27I and p.E114G, both detected at high frequency in probands and controls. The p.E114G variant was always in cis with p.V27I, and formed the haplotype, p.[V27I; E114G] in the Fujian population. Interestingly, only 17.76% (19/107) of NSHL probands had clearly defined pathogenic mutations in GJB2, indicating that the pathogenesis of NSHL in the Fujian population is heterogenous, and that further analysis of other NSHL genes is necessary.