Cited by 408DNA Repair MechanismsBlood disorders and treatmentsGenomics and Rare Diseases

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

Vaz, Fiona, Hanenberg, Helmut, Schuster, Beatrice, Barker, Karen, Wiek, Constanze, Erven, Verena, Neveling, Kornelia, Endt, Daniela +12 more·2010·Nature Genetics

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.

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Crossref · 10.1038/ng.570

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  • RAD51C mutations occur in breast cancer and in a consanguineous family with severe congenital abnormalities characteristic of Fanconi anemia.

    “Conceivably, RAD51C will also join the BRCA-FA family given that mutations were found not only in breast cancer [21], but also in a consanguineous family with severe congenital abnormalities characteristic of FA [31].”

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Authors
Vaz, F., Hanenberg, H., Schuster, B., Barker, K., Wiek, C., Erven, V., Neveling, K., Endt, D., Kesterton, I., Autore, F., Fraternali, F., Freund, M., Hartmann, L., Grimwade, D., Roberts, R. G., Schaal, H., Mohammed, S., Rahman, N., Schindler, D., & Mathew, C. G.
Affiliations
  • Guy's Hospital (GB)
  • Riley Hospital for Children (US)
  • University of Würzburg (DE)
  • Institute of Cancer Research (GB)
  • Heinrich Heine University Düsseldorf (DE)
  • National Health Service (GB)
Corresponding author
  • Hanenberg, Helmut
  • Schindler, Detlev
  • Mathew, Christopher G
Venue
Nature Genetics
Published
2010-04-18
Volume
42
Issue
5
Pages
406-409
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2151206132
Cited by
408
References
31
Citations by year
2026: 4 · 2025: 5 · 2024: 12 · 2023: 11 · 2022: 17 · 2021: 9 · 2020: 22 · 2019: 11 · 2018: 17 · 2017: 18 · 2016: 38 · 2015: 30 · 2014: 31 · 2013: 45 · 2012: 50
FWCI
23.62
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
Cancer Research UK
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
RAD51C, Fanconi anemia, germline mutations, missense mutations, homologous recombination, DNA repair, interstrand cross-linking, mitomycin C sensitivity, camptothecin sensitivity, consanguinity, congenital malformations, chromosomal instability, topoisomerase I inhibitor
MeSH terms
Child, Consanguinity, DNA Damage, DNA Repair, DNA-Binding Proteins, Family Health, Fanconi Anemia, Female, Homozygote, Humans, Infant, Infant, Newborn, Male, Mutation, Pedigree, Recombination, Genetic, Germ-Line Mutation, Mutation, Missense

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