Genetic and Epidemiological Insights into RAB32-Linked Parkinson's Disease.
Parkinson's disease
RAB32
epidemiology
haplotype
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
revised:
18
09
2024
received:
02
07
2024
accepted:
09
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
26
10
2024
Statut:
aheadofprint
Résumé
The p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD). The aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD. We queried our proprietary database that contains exome/genome sequencing data of >180,000 individuals. Additional PD patients were genotyped, and proximal p.Ser71Arg-associated haplotypes were constructed. p.Ser71Arg was present in 11 PD patients (73% from northern Italy) and in 35 individuals (89% from the Middle East and North Africa [MENA]) aged <50 years without PD-relevant symptoms. It was found in-cis to a set of proximal single-nucleotide polymorphisms. Additional RAB32 variants were comparably frequent in PD and non-PD individuals. The RAB32 p.Ser71Arg variant defines a cluster of PD patients in northern Italy. Globally, it is most prevalent in MENA. Our data indicate that p.Ser71Arg causes PD and that it occurred only once, through a founder event. Other RAB32 variants are unlikely to cause PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
BACKGROUND
The p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD).
OBJECTIVE
OBJECTIVE
The aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD.
METHODS
METHODS
We queried our proprietary database that contains exome/genome sequencing data of >180,000 individuals. Additional PD patients were genotyped, and proximal p.Ser71Arg-associated haplotypes were constructed.
RESULTS
RESULTS
p.Ser71Arg was present in 11 PD patients (73% from northern Italy) and in 35 individuals (89% from the Middle East and North Africa [MENA]) aged <50 years without PD-relevant symptoms. It was found in-cis to a set of proximal single-nucleotide polymorphisms. Additional RAB32 variants were comparably frequent in PD and non-PD individuals.
CONCLUSIONS
CONCLUSIONS
The RAB32 p.Ser71Arg variant defines a cluster of PD patients in northern Italy. Globally, it is most prevalent in MENA. Our data indicate that p.Ser71Arg causes PD and that it occurred only once, through a founder event. Other RAB32 variants are unlikely to cause PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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