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

Br J Haematol. 2000 Oct;111(1):338-43. doi: 10.1046/j.1365-2141.2000.02323.x.

Abstract

Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A-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: (1) 2172-2173insG (exon 24), the first 'Moroccan mutation': (2) 4275delT (exon 43), the second 'Moroccan mutation'; (3) 890-893del (exon 10), the 'Tunisian mutation'; and (4) 2574C > G (S858R), the 'Indian mutation'. The tetranucleotide CCTG motif, previously identified as a mutation 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 account for the majority (88%) of the FANCA alleles in the Israeli Jewish (non-Ashkenazi) FA population. A screening of 300 Moroccan Jews identified three carriers of the first 'Moroccan mutation', but we did not find any carrier of the second 'Moroccan mutation' among 140 Moroccan Jews, nor any carrier of the 'Tunisian mutation' among 50 Tunisian Jews. Two 'Indian mutation' carriers were identified among 53 Indian Jews. All carriers within each ethnic group had the same haplotype, suggesting a common founder for each mutation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cell Cycle Proteins*
  • Child
  • Child, Preschool
  • DNA-Binding Proteins*
  • Ethnic Groups*
  • Fanconi Anemia / genetics*
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Genotype
  • Humans
  • India / ethnology
  • Infant
  • Israel
  • Jews*
  • Male
  • Morocco / ethnology
  • Mutation
  • Nuclear Proteins*
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Sequence Analysis, DNA
  • Tunisia / ethnology

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • Proteins