Repeat instability as the basis for human diseases and as a potential target for therapy

Several human neurological and neuromuscular diseases are caused by the expansion of repetitive DNA tracts. Understanding the DNA metabolic processes responsible for the expansion (or lengthening) and contraction (or shortening) of DNA repeats might open new therapeutic avenues for the treatment of these diseases. Expansions of repetitive DNA sequences cause numerous human neurological and neuromuscular diseases. Ongoing repeat expansions in patients can exacerbate disease progression and severity. As pathogenesis is connected to repeat length, a potential therapeutic avenue is to modulate disease by manipulating repeat expansion size — targeting DNA, the root-cause of symptoms. How repeat instability is mediated by DNA replication, repair, recombination, transcription and epigenetics may explain its contribution to pathogenesis and give insights into therapeutic strategies to block expansions or induce contractions.