Reduction of the Supt4h or Supt5h concentration by an amount that only marginally alters overall transcript production can prominently affect the ability of RNAPII to proceed through DNA regions containing expanded nucleotide repeats, and dependence on Supt4h or Supt5h for efficient transcript production has been observed for mutated alleles of the HTT gene (16–19), the orf72 locus on human chromosome 9 (i.e. C9orf72 (20,21)) and the NOP56 gene (22)—which are associated respectively with Huntington's Disease, amyotrophic lateral sclerosis and frontotemporal dementia, and SCA36 type ataxia. Here, HTT is linked to juvenile Huntington disease.