Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration.
DEMENTIA
HUNTINGTON'S
MOVEMENT DISORDERS
NEUROGENETICS
Journal
Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R
Informations de publication
Date de publication:
23 Oct 2024
23 Oct 2024
Historique:
received:
26
02
2024
accepted:
28
09
2024
medline:
24
10
2024
pubmed:
24
10
2024
entrez:
23
10
2024
Statut:
aheadofprint
Résumé
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 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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
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.
RESULTS
RESULTS
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
CONCLUSIONS
CONCLUSIONS
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.
Identifiants
pubmed: 39443079
pii: jnnp-2024-333602
doi: 10.1136/jnnp-2024-333602
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.