title: Mutation of the RAD51C gene in a Fanconi anemia-like disorder.
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.
authors.affiliation: Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Vaz
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Beatrice
authors.initials: B
authors.lastname: Schuster
authors.forename: Karen
authors.initials: K
authors.lastname: Barker
authors.forename: Constanze
authors.initials: C
authors.lastname: Wiek
authors.forename: Verena
authors.initials: V
authors.lastname: Erven
authors.forename: Kornelia
authors.initials: K
authors.lastname: Neveling
authors.forename: Daniela
authors.initials: D
authors.lastname: Endt
authors.forename: Ian
authors.initials: I
authors.lastname: Kesterton
authors.forename: Flavia
authors.initials: F
authors.lastname: Autore
authors.forename: Franca
authors.initials: F
authors.lastname: Fraternali
authors.forename: Marcel
authors.initials: M
authors.lastname: Freund
authors.forename: Linda
authors.initials: L
authors.lastname: Hartmann
authors.forename: David
authors.initials: D
authors.lastname: Grimwade
authors.forename: Roland G
authors.initials: RG
authors.lastname: Roberts
authors.forename: Heiner
authors.initials: H
authors.lastname: Schaal
authors.forename: Shehla
authors.initials: S
authors.lastname: Mohammed
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
mesh_terms: D002648:Child; D003241:Consanguinity; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D011995:Recombination, Genetic
chemical_list: D004268:DNA-Binding Proteins; C448305:RAD51C protein, human
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