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DNA repair in trinucleotide repeat ataxias
Author(s) -
Yau Wai Yan,
O'Connor Emer,
Sullivan Roisin,
Akijian Layan,
Wood Nicholas W.
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14644
Subject(s) - trinucleotide repeat expansion , spinocerebellar ataxia , frataxin , genetics , biology , dna repair , ataxia , epigenetics , cerebellar ataxia , cerebellum , gene , neuroscience , allele , iron binding proteins
The inherited cerebellar ataxias comprise of a genetic heterogeneous group of disorders. Pathogenic expansions of cytosine–adenine–guanine ( CAG ) encoding polyglutamine tracts account for the largest proportion of autosomal dominant cerebellar ataxias, while GAA expansion in the first introns of frataxin gene is the commonest cause of autosomal recessive cerebellar ataxias. Currently, there is no available treatment to alter the disease trajectory, with devastating consequences for affected individuals. Inter‐ and Intrafamily phenotypic variability suggest the existence of genetic modifiers, which may become targets amendable to treatment. Recent studies have demonstrated the importance of DNA repair pathways in modifying spinocerebellar ataxia with CAG repeat expansions. In this review, we discuss the mechanisms in which DNA repair pathways, epigenetics and other genetic factors may act as modifiers in cerebellar ataxias due to trinucleotide repeat expansions.