ReviewJournal of Huntington's disease2021
What is the Pathogenic CAG Expansion Length in Huntington's Disease?
Review in Journal of Huntington's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Reduced CAG Repeats in the Androgen Receptor Gene May Independently Cause Polycystic Ovarian Syndrome.Current issues in molecular biology · 2026Review
- Therapeutic strategies for Huntington's disease: current approaches and future direction.Neurodegenerative disease management · 2026Review
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- Genetic Profiling of Huntington's Disease: Insights from CAG Repeat Analysis for Precision Diagnosis and Management.Noro psikiyatri arsivi · 2026Article
- Rationally Engineered Small Molecules: Pharmacophore Modeling and Molecular Docking Studies Targeting Toxic Polyglutamine (PolyQ) Repeats in Huntington's Disease.Current drug targets · 2026Article
- Integrating CRISPR/Cas technology with clinical trials: Principles, progress and challenges.Asian journal of pharmaceutical sciences · 2025Review
- Intervention Role of APOE in CNS Diseases: APOE Actions and APOE Neurogenesis Capability.Molecular neurobiology · 2025Review
- Impaired nick recognition and ligation efficiency by LIG1 K845N variant linked to Huntington's disease.NAR molecular medicine · 2025Article
- BA9 Transcriptomics in Huntington's Disease 80-Gene Signature and MIR219A2-Linked Targets.International journal of molecular sciences · 2025Article
- Article
- Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.Nature medicine · 2025Observational
- Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state.Nature communications · 2024Article
- Neuroprotective effects of levothyroxine on cognition deficits and memory in an experimental model of Huntington's disease in rats: An electrophysiological study.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Huntingtin is an RNA binding protein and participates inScience advances · 2024Article
- Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype.European journal of human genetics : EJHG · 2024Article
- Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease.American journal of human genetics · 2024Article
- Huntingtin HTT1a is generated in a CAG repeat-length-dependent manner in human tissues.Molecular medicine (Cambridge, Mass.) · 2024Article
- Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease.Journal of Huntington's disease · 2024Article
- Genetic modifiers of repeat expansion disorders.Emerging topics in life sciences · 2023Article
- The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
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5 authors.
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Abstract
Huntington's disease (HD) (OMIM 143100) is caused by an expanded CAG repeat tract in the HTT gene. The inherited CAG length is known to expand further in somatic and germline cells in HD subjects. Age at onset of the disease is inversely correlated with the inherited CAG length, but is further modulated by a series of genetic modifiers which are most likely to act on the CAG repeat in HTT that permit it to further expand. Longer repeats are more prone to expansions, and this expansion is age dependent and tissue-specific. Given that the inherited tract expands through life and most subjects develop disease in mid-life, this implies that in cells that degenerate, the CAG length is likely to be longer than the inherited length. These findings suggest two thresholds- the inherited CAG length which permits further expansion, and the intracellular pathogenic threshold, above which cells become dysfunctional and die. This two-step mechanism has been previously proposed and modelled mathematically to give an intracellular pathogenic threshold at a tract length of 115 CAG (95% confidence intervals 70- 165 CAG). Empirically, the intracellular pathogenic threshold is difficult to determine. Clues from studies of people and models of HD, and from other diseases caused by expanded repeat tracts, place this threshold between 60- 100 CAG, most likely towards the upper part of that range. We assess this evidence and discuss how the intracellular pathogenic threshold in manifest disease might be better determined. Knowing the cellular pathogenic threshold would be informative for both understanding the mechanism in HD and deploying treatments.
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