TY - JOUR
T1 - A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51
AU - Ameziane, Najim
AU - May, Patrick
AU - Haitjema, Anneke
AU - Van De Vrugt, Henri J.
AU - Van Rossum-Fikkert, Sari E.
AU - Ristic, Dejan
AU - Williams, Gareth J.
AU - Balk, Jesper
AU - Rockx, Davy
AU - Li, Hong
AU - Rooimans, Martin A.
AU - Oostra, Anneke B.
AU - Velleuer, Eunike
AU - Dietrich, Ralf
AU - Bleijerveld, Onno B.
AU - Altelaar, Maarten
AU - Meijers-Heijboer, Hanne
AU - Joenje, Hans
AU - Glusman, Gustavo
AU - Roach, Jared
AU - Hood, Leroy
AU - Galas, David
AU - Wyman, Claire
AU - Balling, Rudi
AU - Den Dunnen, Johan
AU - De Winter, Johan P.
AU - Kanaar, Roland
AU - Gelinas, Richard
AU - Dorsman, Josephine C.
PY - 2015/12/18
Y1 - 2015/12/18
N2 - 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-Rffrt ', 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.
AB - 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-Rffrt ', 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.
UR - http://www.scopus.com/inward/record.url?scp=84950244546&partnerID=8YFLogxK
U2 - 10.1038/ncomms9829
DO - 10.1038/ncomms9829
M3 - Article
AN - SCOPUS:84950244546
SN - 2041-1723
VL - 6
JO - Nature Communications [E]
JF - Nature Communications [E]
M1 - 8829
ER -