Mutation of the RAD51C gene in a Fanconi anemia-like disorder

  • Nat Genet. 2010 May;42(5):406-9. doi: 10.1038/ng.570.
Fiona Vaz  1 ,  Helmut Hanenberg ,  Beatrice Schuster ,  Karen Barker ,  Constanze Wiek ,  Verena Erven ,  Kornelia Neveling ,  Daniela Endt ,  Ian Kesterton ,  Flavia Autore ,  Franca Fraternali ,  Marcel Freund ,  Linda Hartmann ,  David Grimwade ,  Roland G Roberts ,  Heiner Schaal ,  Shehla Mohammed ,  Nazneen Rahman ,  Detlev Schindler ,  Christopher G Mathew
Affiliations
  • 1. Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, UK.
PMID: 20400963 DOI: 10.1038/ng.570
Abstract

Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and Other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome.