A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51.

TitleA novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51.
Publication TypeJournal Article
Year of Publication2015
AuthorsAmeziane N, May P, Haitjema A, van de Vrugt HJ, van Rossum-Fikkert SE, Ristic D, Williams GJ, Balk J, Rockx D, Li H, Rooimans MA, Oostra AB, Velleuer E, Dietrich R, Bleijerveld OB, Altelaar AFMaarten, Meijers-Heijboer H, Joenje H, Glusman G, Roach J, Hood L, Galas D, Wyman C, Balling R, den Dunnen J, de Winter JP, Kanaar R, Gelinas R, Dorsman JC
JournalNat Commun
Date Published2015 Dec 18
KeywordsBase Sequence, DNA Damage, DNA Repair, DNA Repair Enzymes, DNA-Binding Proteins, Fanconi Anemia, Humans, Male, Molecular Sequence Data, Mutation, Missense, Recombination, Genetic, Young Adult
Abstract<p>Fanconi anaemia (FA) is a hereditary disease featuring hypersensitivity to DNA cross-linker-induced chromosomal instability in association with developmental abnormalities, bone marrow failure and a strong predisposition to cancer. A total of 17 FA disease genes have been reported, all of which act in a recessive mode of inheritance. Here we report on a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in one allele of the homologous recombination DNA repair gene RAD51 in an FA-like patient. This heterozygous mutation causes a novel FA subtype, 'FA-R', which appears to be the first subtype of FA caused by a dominant-negative mutation. The patient, who features microcephaly and mental retardation, has reached adulthood without the typical bone marrow failure and paediatric cancers. Together with the recent reports on RAD51-associated congenital mirror movement disorders, our results point to an important role for RAD51-mediated homologous recombination in neurodevelopment, in addition to DNA repair and cancer susceptibility.</p>
Alternate JournalNat Commun
PubMed ID26681308
PubMed Central IDPMC4703882