Tsukada K, Nishio S, Usami S, and the Deafness Gene Study Consortium. A large cohort study of GJB2 mutations in Japanese hearing loss patients.
GJB2 is the gene most frequently associated with hereditary hearing loss, and the GJB2 mutation spectrums vary among different ethnic groups. In this study, the mutation spectrum as well as clinical features of patients with GJB2 mutations as found in more than 1000 Japanese hearing loss families are summarized. The present results show that the frequency of GJB2 mutations in the Japanese population with hearing loss is 14.2% overall and 25.2% in patients with congenital hearing loss. c.235delC was the most frequent allele (49.8%), was associated with a more severe phenotype, and was mainly found in patients who were diagnosed by the age of 3. In contrast, the second most frequent was p.V37I (16.5%), which has a milder phenotype and was mainly found in patients diagnosed at a higher age. Additional clinical features in hearing loss patients with GJB2 mutations in this study were the near absence of tinnitus, vestibular dysfunction and inner ear malformations.