Recent studies supported a role for somatic instability in disease pathogenesis implicating FAN1 and MMR proteins as modifiers of the age of onset in Huntington disease (Lee et al., 2015, 2017; Deshmukh A. et al., 2021b, Deshmukh et al., 2021 A. L.a; Porro et al., 2021) and spinocerebellar ataxias (SCAs) (Bettencourt et al., 2016), and alteration of MMR is sufficient to overturn somatic instability and can moderate toxicity in Huntington disease mice (Kovalenko et al., 2012; Pinto et al., 2013). This evidence concerns the gene MRC1 and juvenile Huntington disease.