THE ASHKENAZI JEWISH FANCONI-ANEMIA MUTATION - INCIDENCE AMONG PATIENTS AND CARRIER FREQUENCY IN THE AT-RISK POPULATION

Fanconi anemia (FA) is an autosomal recessive disease for which at lea st four complementation groups exist. Recently the gene that corrects the defect in Fanconi anemia complementation group C cells (FACC) has been cloned. We have previously identified a common mutation in the FA CC gene, which accounts for a majority of FA cases in Ashkenazi Jewish individuals. We here describe the use of allele-specific oligonucleot ide (ASO) hybridization to determine the frequency of this mutation am ong additional Jewish FA patients and to determine the carrier frequen cy in the Jewish population. The common IVS4 + 4A --> T allele was fou nd on 19/23 (83%) Jewish FA chromosomes, indicating that it is indeed responsible for most cases of FA among Ashkenazi Jews. The carrier fre quency was 2/314 for Jewish individuals and the mutant allele was not detected in 130 non-jewish controls. (C) 1994 Wiley-Liss, Inc.