Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns

• Published in: Journal of human genetics Vol. 50; no. 2; pp. 76 - 83
• Main Authors: Oguchi, Tomohiro, Ohtsuka, Akihiro, Hashimoto, Shigenari, Oshima, Aki, Abe, Satoko, Kobayashi, Yumiko, Nagai, Kyoko, Matsunaga, Tatsuo, Iwasaki, Satoshi, Nakagawa, Takashi, Usami, Shin-Ichi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-02-2005
• Subjects: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Connexin 26; Connexins - genetics; Deafness; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Genetic screening; Genotype; Genotypes; Hearing loss; Hearing Loss - genetics; Humans; Infant; Infant, Newborn; Male; Middle Aged; Missense mutation; Mutation; Phenotype; Phenotypes; Population genetics; Prognosis; Protein expression; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1007/s10038-004-0223-7

Mutations in the GJB2 (connexin 26, Cx26) gene are the major cause of nonsyndromic hearing impairment in many populations. Genetic testing offers opportunities to determine the cause of deafness and predict the course of hearing, enabling the prognostication of language development. In the current study, we compared severity of hearing impairment in 60 patients associated with biallelic GJB2 mutations and assessed the correlation of genotypes and phenotypes. Within a spectrum of GJB2 mutations found in the Japanese population, the phenotype of the most prevalent mutation, 235delC, was found to show more severe hearing impairment than that of V37I, which is the second most frequent mutation. The results of the present study, taken together with phenotypes caused by other types of mutations, support the general rule that phenotypes caused by the truncating GJB2 mutations are more severe than those caused by missense mutations. The present in vitro study further confirmed that differences in phenotypes could be explained by the protein expression pattern.