Mutation of the RAD51C gene in a Fanconi anemia-like disorder.
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.
Vaz
Fiona
F
Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, UK.
Hanenberg
Helmut
H
Schuster
Beatrice
B
Barker
Karen
K
Wiek
Constanze
C
Erven
Verena
V
Neveling
Kornelia
K
Endt
Daniela
D
Kesterton
Ian
I
Autore
Flavia
F
Fraternali
Franca
F
Freund
Marcel
M
Hartmann
Linda
L
Grimwade
David
D
Roberts
Roland G
RG
Schaal
Heiner
H
Mohammed
Shehla
S
Rahman
Nazneen
N
Schindler
Detlev
D
Mathew
Christopher G
CG
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
D004268:DNA-Binding Proteins; C448305:RAD51C protein, human
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