Positional cloning of the Fanconi anaemia group A gene

Nat Genet. 1996 Nov;14(3):324-8. doi: 10.1038/ng1196-324.


Fanconi anaemia (FA) is an autosomal recessive disorder associated with progressive bone-marrow failure, a variety of congenital abnormalities, and predisposition to acute myeloid leukaemia. Cells from FA patients show increased sensitivity to bifunctional DNA crosslinking agents such as diepoxybutane and mitomycin C, with characteristic chromosome breakage. FA is genetically heterogeneous, at least five different complementation groups (FA-A to FA-E) having been described. The gene for group C (FAC) was cloned by functional complementation and mapped to chromosome 9q22.3 (refs 3, 5), but the genes for the other complementation groups have not yet been identified. The group A gene (FAA) has recently been mapped to chromosome 16q24.3 by linkage analysis, and accounts for 60-65% of FA cases. We narrowed the candidate region by linkage and allelic association analysis, and have isolated a gene that is mutated in FA-A patients. The gene encodes a protein of 1,455 amino acids that has no significant homology to any other known proteins, and may therefore represent a new class of genes associated with the prevention or repair of DNA damage.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Cycle Proteins*
  • Chromosome Mapping
  • Cloning, Molecular / methods
  • DNA-Binding Proteins*
  • Fanconi Anemia / epidemiology
  • Fanconi Anemia / genetics*
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • Gene Deletion
  • Genetic Linkage
  • Haplotypes
  • Heterozygote
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Nuclear Proteins*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Sequence Analysis, DNA
  • Tissue Distribution


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • FANCC protein, human
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • Proteins

Associated data

  • GENBANK/R07212
  • GENBANK/R07213
  • GENBANK/R60950
  • GENBANK/R61618