Evidence of a founder effect for the 235delC mutation of GJB2 (connexin 26) in east Asians.

Mutations in the GJB2 gene encoding connexin 26 (Cx26) are a major cause of autosomal recessive and sporadic cases of congenital deafness in most populations. The 235delC mutation of GJB2 is the most frequent known mutation in some east Asian populations, with a carrier frequency of approximately 1%. In order to study the origin of 235delC among east Asians, we analyzed single-nucleotide polymorphisms (SNPs) within the coding region of GJB2 and flanking the 235delC mutation. We observed significant linkage disequilibrium between 235delC and five linked polymorphic markers, suggesting that 235delC arose from a common founder. The detection of 235delC only in east Asians, but not in Caucasians, and the small chromosomal interval of the shared haplotype suggest that 235delC is an ancient mutation that arose after the divergence of Mongoloids and Caucasians. Similarly, the finding that this mutation appears on a single haplotype provides no support for the possibility that recurrent mutation is the explanation for the high frequency of the allele.