Fanconi anaemia group A (FANCA) mutations in Israeli non-Ashkenazi Jewish patients

Fanconi anaemia (FA) is a genetically heterogeneous disease with at least e ight complementation groups (A-H). In the present study, we investigated th e molecular basis of the disease in 13 unrelated Israeli Jewish (non-Ashken azi) patients with EA. All 43 exons of the Fanconi anaemia A (FANCA) gene w ere amplified from genomic DNA and screened for mutations by single-strand conformation polymorphism and DNA sequencing. We identified four ethnic-spe cific mutations: (1) 2172-2173insG (exon 24), the first 'Moroccan mutation' ; (2) 4275delT (exon 43), the second 'Moroccan mutation'; (3) 890-893del (e xon 10), the 'Tunisian mutation'; and (4) 2574C > G (S858R), the 'Indian mu tation'. The tetranucleotide CCTG motif, previously identified as a mutatio n hotspot in FANCA and other human genes, was found in the vicinity of 2172 -2173insG and 890-893del. According to our study, the four mutations accoun t for the majority (88%) of the FANCA alleles in the Israeli Jewish (non-As hkenazi) FA population. A screening of 300 Moroccan Jews identified three c arriers of the first 'Moroccan mutation', but we did not find any carrier o f the second 'Moroccan mutation' among 140 Moroccan Jews, nor any carrier o f the 'Tunisian mutation' among 50 Tunisian Jews. Two 'Indian mutation' car riers were identified among 53 Indian Jews. All carriers within each ethnic group had the same haplotype, suggesting a common founder for each mutatio n.