Nature communications · 2015
A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, Maarten Altelaar A F, 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, Dorsman Josephine C
Аннотация
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.