The crucial role of gap junctions; which are composed of connexin (CX) protein; in auditory functions has been confirmed by numerous studies. In this study; we investigate the prevalence and phenotype/genotype correlation of connexin (CX) gene family variants in a cohort of children with nonsyndromic hearing loss (HL). A total of 253 unrelated children with nonsyndromic HL were screened for the presence of variants in 6 genes of the CX gene family. The prevalence of CX gene variants in 253 patients was 19.7% (50/253). We found the frequency of a sloping audiometric configuration was significantly higher for children with GJB2 and GJB3 variants than for those with GJB4 and GJC3 variants (Adjusted OR = 4.89; p < 0.001). Conversely; the frequency of a flat audiometric configuration was significantly higher for children with GJB4 and GJC3 variants than for those with GJB2 and GJB3 variants (adjusted OR = 7.76; p < 0.001). The relative frequencies of multiplex families was significantly higher for children with GJB3 variants than for those with GJB2; GJB4; and GJC3 variants (Adjusted OR = 11.33; p = 0.003). Our results suggest the variants of GJC3; GJB4; and GJB3 may be the common genetic risk factor; after variants of GJB2; for the development of nonsyndromic HL in Taiwan. These data can be effectively applied to direct the clinical evaluation of children with CX gene variants.
