Genetic and Epidemiological Insights into <scp><i>RAB32</i></scp>‐Linked Parkinson's Disease
Mandy Radefeldt, Sabrina Lemke, Kridsadakorn Chaichoompu, Jefri Jeya Paul, Filipa Curado, Franco Valzania, Francesco Cavallieri, Valentina Fioravanti, Enza Maria Valente, Micol Avenali, Anna Negrotti, Haşmet Hanağası, Sven Thonke, Michele Matarazzo, Andrea Panzavolta, Chiara Cerami, Ana Westenberger, Christine Klein, Peter Bauer, Christian Beetz
Abstract
BACKGROUND: The p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD). OBJECTIVE: The aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD. 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: 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: 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.