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         headline:A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51
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      headline:A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51
      description: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. Fanconi anaemia is an inherited disorder characterised by developmental abnormalities, bone marrow failure and predisposition to cancer. Here the authors report a de novo mutation in the DNA repair gene Rad51in an atypical subtype of Fanconi anaemia.
      datePublished:2015-12-18T00:00:00Z
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