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

作者：Ameziane Najim; May Patrick; Haitjema Anneke; van de Vrugt Henri J; van Rossum Fikkert Sari E; Ristic Dejan; Williams Gareth J; Balk Jesper; Rockx Davy; Li Hong; Rooimans Martin A; Oostra Anneke B; Velleuer Eunike; Dietrich Ralf; Bleijerveld Onno B; Altelaar A F Maarten; Meijers Heijboer Hanne; Joenje Hans; Glusman Gustavo; Roach Jared; Hood Leroy; Galas David; Wyman Claire; Balling Rudi; den Dunnen Johan; de Winter Johan P; Kanaar Roland; Gelinas Richard^*

来源：Nature Communications, 2015, 6(1): 8829.

DOI：10.1038/ncomms9829

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.

• 出版日期2015-12