Nonradioactive detection. of the common Connexin 26 167delT and 35delG mutations and frequencies among Ashkenazi Jews

Mutations in the gap junction beta2 (GJB2) gene, Connexin 26 (Cx26), cause nonsyndromic sensorineural recessive deafness (NSRD). Two frameshift mutati ons, 167delT and 35delG, are the most frequent Cx26 lesions causing NSRD. T he 35delG mutation is panethnic, while the 167delT lesion occurs almost exc lusively in the Ashkenazi Jewish population at a carrier frequency of 2 to 4%. To facilitate carrier detection, a simple nonradioactive allele-specifi c oligonucleotide (ASO) hybridization assay was developed for the 167delT a nd 35delG mutations. Screening of 1012 anonymous Ashkenazi Jewish individua ls from the New York Metropolitan area revealed carrier frequencies for 167 delT and 35delG of 3.96% (95% CI: 2.75-5.15%) and 0.69% (95% CI: 0.18-1.20% ), respectively. This sensitive, specific, and relatively inexpensive metho d can reliably identify affected newborns and patients with NSRD as well as facilitate carrier screening for Conexin 26 deafness in the Ashkenazi Jewi sh community. (C) 2001 Academic Press.