Determination of the carrier frequency of the common GJB2 (Connexin-26) 35delG mutation in the Belgian population using an easy and reliable screening method

Mutations in the gene GJB2, encoding the gap-junction protein connexin-26, have been shown to be a major cause of nonsyndromic recessive deafness (NSR D). A single mutation in the GJB2 gene accounts for the majority of NSRD in many different populations. This mutation represents a deletion of a guani ne within a stretch of six Gs between nucleotide positions +30 and +35 of t he GJB2 cDNA (35delG). Molecular detection of the 35delG mutation is usuall y performed by direct sequencing analysis of PCR products, or by allele spe cific PCR analysis. To screen for this mutation, we developed an easier and more reliable method, based on the principle of PCR mediated site-directed mutagenesis (PSDM), followed by a BsiYI digestion. We tested 360 unrelated unaffected Belgian individuals for heterozygosity of the 35delG mutation a nd found a carrier frequency of 1 in 40 (95% CI, 1 in 30 to 1 in 60). As ou r new screening method is simple and reliable in use, and detects a mutatio n responsible for a significant part of NSRD, it may find widespread use in DNA diagnostics. Hum Mutat 14:263-266, 1999. (C) 1999 Wiley-Liss, Inc.