17-20 That the variants affected the function of these DNA repair genes was supported by previous experiments showing that the ablation of specific mismatch repair genes (Msh2, Msh3, Mlh1 and Mlh3) reduced somatic CAG repeat instability in mouse models of Huntington's disease.21-23 Mechanistically, it has since been shown that FAN1 nuclease activity is implicated in slowing CAG repeat expansion,24 that the promotion of somatic CAG instability by FAN1 is blocked in the absence of MLH125 and that FAN1 controls mismatch repair assembly via MLH1 to stabilize the CAG repeat.26,27. Here, MLH1 is linked to juvenile Huntington disease.