DNA repair gene mutation leads to anemia!

DNA repair gene mutation leads to anemia!

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. Researchers 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, these results point to an important role for RAD51-mediated homologous recombination in neurodevelopment, in addition to DNA repair and cancer susceptibility.