Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population

Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction prot ein and is expressed in the inner ear, have been shown to be responsible fo r a major part of nonsyndromic hereditary prelingual (early-childhood) deaf ness in Caucasians. We have sequenced the GJB2 gene in 39 Japanese patients with prelingual deafness (group 1), 39 Japanese patients with postlingual progressive sensorineural hearing loss (group 2), and 63 Japanese individua ls with normal hearing (group 3), Three novel mutations were identified in group 1: a single nucleotide deletion (235delC), a 16-bp deletion (176-191 del (16)), and a nonsense mutation (Y136X) in five unrelated patients. The 235delC mutation was most frequently observed, accounting for seven alleles in 10 mutant alleles. Screening of 203 unrelated normal individuals for th e three mutations indicated that the carrier frequency of the 235delC mutat ion was 2/203 in the Japanese population. No mutation was found in group-a patients, We also identified two novel polymorphisms (E114G and I203T) as w ell as two previously reported polymorphisms (V27I and V37I), Genotyping wi th these four polymorphisms allowed normal Japanese alleles to be classifie d into seven haplotypes, All 235delC mutant alleles identified in four pati ents resided only on haplotype type 1, These findings indicate that GJB2 mu tations are also responsible for prelingual deafness in Japan, Am. J, Med, Genet. 90:141-145, 2000. (C) 2000 Wiley-Liss, Inc.