In HD, somatic instability is influenced by polymorphisms in MSH3, MLH1, MlH3, and FAN1, which are all involved in DNA repair (Ciosi et al., 2019). Counterintuitively, loss of function of some DNA repair factors can be protective: knockout of Msh2 or Msh3 in a knock-in model of HD prevents CAG expansions in the striatum (Pinto et al., 2013). This evidence concerns the gene MLH1 and Huntington disease.