Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration

Koriath, Carolin Anna Maria, Guntoro, Fernando, Norsworthy, Penelope, Dolzhenko, Egor, Eberle, Michael, Hensman Moss, Davina J, Flower, Michael, Hummerich, Holger, Rosser, Anne Elizabeth ORCID: https://orcid.org/0000-0002-4716-4753, Tabrizi, Sarah J, Mead, Simon and Wild, Edward J 2024. Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration. Journal of Neurology, Neurosurgery and Psychiatry 10.1136/jnnp-2024-333602

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Abstract

Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC. Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis. HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one expansion in a patient with HDPC. The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC. [Abstract copyright: © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.]

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine
Publisher:	BMJ Publishing Group
ISSN:	0022-3050
Date of First Compliant Deposit:	6 November 2024
Date of Acceptance:	28 September 2024
Last Modified:	06 Nov 2024 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/173695

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