Prospective variants screening of connexin genes in children with hearing impairment: genotype/phenotype correlation.
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.
Yang
Jiann-Jou
JJ
Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC.
Wang
Wen-Hung
WH
Lin
Yen-Chun
YC
Weng
Hsu-Huei
HH
Yang
Jen-Tsung
JT
Hwang
Chung-Feng
CF
Wu
Che-Min
CM
Li
Shuan-Yow
SY
D002648:Child; D015331:Cohort Studies; D000072259:Connexin 26; D000075302:Connexin 30; D018031:Connexin 43 / Q000235:genetics; D017630:Connexins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D014644:Genetic Variation; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D005810:Multigene Family; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011446:Prospective Studies; D013624:Taiwan
D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C500216:GJA1 protein, human; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; C464674:GJC3 protein, human; D009419:Nerve Tissue Proteins; D000072259:Connexin 26; C068044:GJB3 protein, human; C076275:connexin 30.3