Fanconi anaemia group A (FANCA) mutations in... : British Journal of Haematology (original) (raw)

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

H. Tamary
R. Bar-Yam
L. Shalmon
G. Rachavi
M. Krostichevsky
R. Elhasid
Y. Barak
J. Kapelushnik
I. Yaniv
A. D. Auerbach
R. Zaizov

British Journal of Haematology

111

(

)

338

343

October 2000

Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A[ndash]H). In the present study, we investigated the molecular basis of the disease in 13 unrelated Israeli Jewish (non-Ashkenazi) patients with FA. All 43 exons of the Fanconi anaemia A (FANCA) gene were amplified from genomic DNA and screened for mutations by single-strand conformation polymorphism and DNA sequencing. We identified four ethnic-specific mutations[colon] (1) 2172[ndash]2173insG (exon 24), the first [lsquo]Moroccan mutation[rsquo]; (2) 4275delT (exon 43), the second [lsquo]Moroccan mutation[rsquo]; (3) 890[ndash]893del (exon 10), the [lsquo]Tunisian mutation[rsquo]; and (4) 2574C [gt] G (S858R), the [lsquo]Indian mutation[rsquo]. The tetranucleotide CCTG motif, previously identified as a mutation hotspot in FANCA and other human genes, was found in the vicinity of 2172[ndash]2173insG and 890[ndash]893del. According to our study, the four mutations account for the majority (88[percnt]) of the FANCA alleles in the Israeli Jewish (non-Ashkenazi) FA population. A screening of 300 Moroccan Jews identified three carriers of the first [lsquo]Moroccan mutation[rsquo], but we did not find any carrier of the second [lsquo]Moroccan mutation[rsquo] among 140 Moroccan Jews, nor any carrier of the [lsquo]Tunisian mutation[rsquo] among 50 Tunisian Jews. Two [lsquo]Indian mutation[rsquo] carriers were identified among 53 Indian Jews. All carriers within each ethnic group had the same haplotype, suggesting a common founder for each mutation.