Genetic and Epidemiological Insights into RAB32-Linked Parkinson's Disease.

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.

Radefeldt M ，Lemke S ，Chaichoompu K ，Paul JJ ，Curado F ，Valzania F ，Cavallieri F ，Fioravanti V ，Valente EM ，Avenali M ，Negrotti A ，Hanagasi HA ，Thonke S ，Matarazzo M ，Panzavolta A ，Cerami C ，Westenberger A ，Klein C ，Bauer P ，Beetz C ... -  《-》

The RAB32 p.Ser71Arg Variant in Parkinsonisms: Insights from a Large Italian Cohort.

Recently, RAB32 has been identified as possibly linked to Parkinson's disease. We studied the prevalence and clinical correlates of the p.Ser71Arg variant in the RAB32 gene in a large case series of Italian patients with Parkinson's disease or atypical parkinsonism. A single-center cohort with a case-control component (consecutively collected at the Parkinson Institute of Milan between 2002 and 2023) was screened for the RAB32 p.Ser71Arg variant. Detailed clinical characteristics of carriers were reviewed. Healthy control subjects were partners or unrelated caregivers. The variant was detected by a TaqMan polymerase chain reaction assay. A total of 4600 patients (3762 with PD and 838 with atypical parkinsonisms) and 1722 healthy control subjects were consecutively included in the study. We identified 20 new variant carriers that, together with the 8 previously identified, had younger age at onset than noncarriers (51.0 ± 10.7 vs. 58.3 ± 11.0 years, respectively; P = 0.01). All carriers had a good response to dopaminergic therapy and device-aided therapies. Carriers had mild or no cognitive decline and mild or no depressive symptoms; six had impulse control disorders and one a REM behavior disorder. Family history was positive in 55.5% of cases versus 22.0% of patients without the variant (P < 0.001) and was compatible with a dominant pattern of inheritance. The variant was not identified in patients with atypical parkinsonisms. This study confirms that RAB32 is associated with a relatively young adult-onset PD with a favorable therapeutic response. This variant should be included in genetic panels used for the diagnosis of familial and/or relatively young-onset PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Magistrelli L ，Brumana M ，Rimoldi V ，Poggi-Longostrevi S ，Contaldi E ，Pezzoli G ，Straniero L ，Isaias IU ，Asselta R ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses.

Gustavsson EK ，Follett J ，Trinh J ，Barodia SK ，Real R ，Liu Z ，Grant-Peters M ，Fox JD ，Appel-Cresswell S ，Stoessl AJ ，Rajput A ，Rajput AH ，Auer R ，Tilney R ，Sturm M ，Haack TB ，Lesage S ，Tesson C ，Brice A ，Vilariño-Güell C ，Ryten M ，Goldberg MS ，West AB ，Hu MT ，Morris HR ，Sharma M ，Gan-Or Z ，Samanci B ，Lis P ，Periñan MT ，Amouri R ，Ben Sassi S ，Hentati F ，Global Parkinson's Genetics Program (GP2) ，Tonelli F ，Alessi DR ，Farrer MJ ... -  《-》

Natural Health Products for Symptomatic Relief of Parkinson's Disease: Prevalence, Interest, and Awareness.

Diadhiou S ，Maas BR ，Schootemeijer S ，Bloem BR ，de Vries NM ，Calon F ，Darweesh SKL ，de Rus Jacquet A ... -  《-》