Sequence Variants in Small CAG Repeat Expansions of the <i>HTT</i> Gene and Disease Onset and Progression in Huntington Disease
In this large cohort, including DNA sequence and phenotypical data, the LOI variant showed a significant modifying effect on AO, motor, and cognitive disease progression. These findings, along with the identification of a novel variant, have important implications for genetic testing and counseling, especially for individuals with expansions close to cutoff ranges. In addition, they underscore the need to integrate the DNA sequence in the diagnostic process and revisit current onset prediction models.
Authors
- Chris Kay (ORCID: https://orcid.org/0000-0002-4381-7438)
- Hailey Findlay Black
- Giulia Coarelli (ORCID: https://orcid.org/0000-0002-7824-8343)
- Alexandra Dürr (ORCID: https://orcid.org/0000-0002-8921-7104)
- Jean‐Loup Méreaux (ORCID: https://orcid.org/0000-0002-4279-7252)
- Emilien Petit (ORCID: https://orcid.org/0009-0000-0602-7122)
- Larissa Arning (ORCID: https://orcid.org/0000-0002-8913-5627)
- Michael R. Hayden (ORCID: https://orcid.org/0000-0001-5159-1419)
- Hortense Hurmic (ORCID: https://orcid.org/0009-0004-4712-1501)
- Sabrina Sayah (ORCID: https://orcid.org/0000-0002-0382-9995)
- Jessica Dawson (ORCID: https://orcid.org/0000-0002-8773-4634)
- Anna Heinzmann (ORCID: https://orcid.org/0000-0001-8522-7199)
- Jérémie Pariente (ORCID: https://orcid.org/0000-0002-9850-296X)
- Huu Phuc Nguyen
- Claire-Sophie Davoine
- Fleur Gérard
Institutions
- Université Toulouse III - Paul Sabatier (FR)
- University of British Columbia (CA)
- Inserm (FR)
- University Hospitals of the Ruhr-University of Bochum (DE)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Sorbonne Université (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Purpan (FR)
- Institut du Cerveau (FR)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Neurology
- Published
- 2025-12-19
- DOI
- https://doi.org/10.1212/wnl.0000000000214404
- Citations
- 1
- Primary Topic
- Genetic Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.91