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

Background and objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.