GJB2 mutation spectrum in the Taiwanese population and genotype-phenotype comparisons in patients with hearing loss carrying GJB2 c.109G>A and c.235delC mutations.

Hearing loss, the most common sensory abnormality, is caused by the death of or damage to inner ear hair cells. Genetic mutations are the main cause of hearing loss. We used nex-generation sequencing data released by the Taiwan Biobank to investigate the GJB2 mutation spectrum in 1517 patients. We compared hearing function in Taiwanese patients with nonsyndromic hearing loss (NSHL) caused by the two most common GJB2 mutations c.109G>A (p.V37I) and c.235delC. We extracted DNA from the oral mucosa of patients with NSHL and performed Sanger sequencing to confirm the genotype. Of 240 patients with NSHL, we identified 25 with GJB2 c.109G>A and 9 with GJB2 c.235delC mutations, after excluding patients aged >10 years, in whom hearing loss may have been caused due to age-related degeneration. We investigated genotype-phenotype correlations in patients harboring GJB2 c.109G>A and c.235delC mutations. Furthermore, we described the GJB2 mutation spectrum in the Taiwanese population and identified the role of homozygous and heterozygous GJB2 mutations associated with hearing phenotypes in patients with NSHL. Thus, our study provides insights into the complexity of GJB2 genetics. Our data indicate that GJB2 c.109G>A heterozygotes had poorer hearing than did homozygotes. The mechanism underlying the more severe phenotype in heterozygotes and whether the phenotype is caused by GJB2 heterozygotes or compound heterozygotes warrant future investigation.