A common founder for the 35deIG GJB2 gene mutation in connexin 26 hearing impairment

Fifty to eighty percent of autosomal recessive congenital severe to profoun d hearing impairment result from mutations in a single gene, GJB2, that enc odes the protein connexin 26. One mutation of this gene, the 35delG allele, is particularly common in white populations. We report evidence that the h igh frequency of this allelic variant is the result of a founder effect rat her than a mutational hot spot in GJB2, which was the prevailing hypothesis . Patients homozygous for the 35delG mutation and normal hearing controls o riginating from Belgium, the UK, and the USA were genotyped for different s ingle nucleotide polymorphisms (SNPs). Four SNPs mapped in the immediate vi cinity of GJB2, while two were positioned up to 76 kb from it. Significant differences between the genotypes of patients and controls for the five SNP s closest to GJB2 were found, with nearly complete association of one SNP a llele with the 35delG mutation. For the most remote SNP, we could not detec t any association. We conclude that the 35delG mutation is derived from a c ommon, albeit ancient founder.