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Clinical implications of loss of interruption variants for diagnosis, genetic counselling, and clinical trials in Huntington's disease

Year: 2026

Type: article

Abstract: Age of onset in Huntington disease (HD) is influenced by cis- acting genetic variants, particularly the loss of interrupting codons in the HTT CAG and CCG repeats (CAG-CCG LOI variant). The CAG-CCG LOI variant is not detectable by current diagnostic assays, leading to underestimation of CAG repeat length, misdiagnosis, and inaccurate prediction of risk of symptom onset in the reduced penetrance range. In clinical trials, unidentified CAG-CCG LOI variants may affect interpretation of results, particularly for small trials. Accurate ascertainment and reporting of the CAG-CCG LOI genotype therefore has important implications for HD diagnosis, genetic counselling, and clinical trial design.

Source: Journal of Huntington s Disease

DOI: 10.1177/18796397261443135

Authors: Hailey Findlay Black, Jessica Levesley, Chris Kay, Stephanie Bortnick, Kyla Javier, Michael R Hayden

Institution: University of British Columbia

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,150