Observational studyAmerican journal of human genetics2016
The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease.
Observational study in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
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Who cites it
83 citing papers in PubMed, 163 citations in OpenAlex.
- DNA methylation profiling in Huntington's disease reveals disease associated changes in the striatum.Clinical epigenetics · 2026Article
- Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders.Handbook of experimental pharmacology · 2026Review
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Article
- Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease.Journal of Huntington's disease · 2025Article
- A digital motor score for sensitive detection of progression in Huntington's disease.Brain : a journal of neurology · 2025Article
- A quadratic paradigm describes the relationship between phenotype severity and variation.Nature communications · 2025Article
- Significant underascertainment in Huntington's disease.Brain communications · 2025Article
- Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.CNS neuroscience & therapeutics · 2024Review
- Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.Journal of clinical neurology (Seoul, Korea) · 2024Article
- Review
- Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease.Pharmaceutics · 2024Article
- Brain-Periphery Interactions in Huntington's Disease: Mediators and Lifestyle Interventions.International journal of molecular sciences · 2024Review
- PSP-Richardson's Syndrome as a Rare Phenotypic Expression of Very Late-Onset Huntington's Disease: A Case Report.Movement disorders clinical practice · 2024Article
- Discovery and engineering of AiEvo2, a novel Cas12a nuclease for human gene editing applications.The Journal of biological chemistry · 2024Article
- Rasch Measurement Theory (RMT) Analyses of the Huntington's Disease Everyday Functioning (Hi-DEF) to Evaluate Item Fit and Performance.Journal of Huntington's disease · 2024Observational
- Genetic modifiers of repeat expansion disorders.Emerging topics in life sciences · 2023Article
- Development of a population pharmacokinetic model to characterize the pharmacokinetics of intrathecally administered tominersen in cerebrospinal fluid and plasma.CPT: pharmacometrics & systems pharmacology · 2023Article
- From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington's Disease Research.International journal of molecular sciences · 2023Review
- Survival in Huntington's disease and other young-onset dementias.International journal of geriatric psychiatry · 2023Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
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 occurs to permit CAG-independent processes and then lead to eventual death. In this scenario, some pathological changes and their clinical correlates could still worsen in a CAG-driven manner after disease onset, but these CAG-related progressive changes do not themselves determine duration. Alternatively, (2) HD pathogenesis is driven by mutant huntingtin acting in a CAG-dependent manner with different time courses in multiple cell types, and the cellular targets that lead to motor onset and death are different and independent. In this scenario, processes driven by HTT CAG length lead directly to death but not via the striatal pathology associated with motor manifestations. Each scenario has important ramifications for the design and testing of potential therapeutics, especially those aimed at preventing or delaying characteristic motor manifestations.
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Registered trials
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