The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease.

ABSTRACT: Huntington disease (HD) is caused by an expanded HTT CAG repeat that leads in a length-dependent, completely dominant manner to onset of a characteristic movement disorder. HD also displays early mortality, so we tested whether the expanded CAG repeat exerts a dominant influence on age at death and on the duration of clinical disease. We found that, as with clinical onset, HD age at death is determined by expanded CAG-repeat length and has no contribution from the normal CAG allele. Surprisingly, disease duration is independent of the mutation's length. It is also unaffected by a strong genetic modifier of HD motor onset. These findings suggest two parsimonious alternatives. (1) HD pathogenesis is driven by mutant huntingtin, but before or near motor onset, sufficient CAG-driven damage occ

SUBMITTER: Keum JW 

PROVIDER: S-EPMC4746370 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature