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

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-12-31 DOI:10.1002/mds.30103

Luca Magistrelli MD, PhD, Marta Brumana MSc, Valeria Rimoldi PhD, Sofia Poggi-Longostrevi MD, Elena Contaldi MD, PhD, Gianni Pezzoli MD, Letizia Straniero PhD, Ioannis U. Isaias MD, PhD, Rosanna Asselta PhD

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Abstract

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.

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帕金森病的RAB32 p.Ser71Arg变异：来自意大利大型队列的见解

背景与目的最近，RAB32被发现可能与帕金森病有关。我们研究了RAB32基因p.Ser71Arg变异在大量意大利帕金森病或非典型帕金森病患者中的患病率和临床相关性。方法对具有病例对照成分的单中心队列（2002年至2023年在米兰帕金森研究所连续收集）进行RAB32 p.Ser71Arg变体筛选。回顾了携带者的详细临床特征。健康对照受试者为伴侣或非亲属照顾者。TaqMan聚合酶链反应法检测该变异。结果共纳入4600例PD患者（3762例，非典型帕金森患者838例）和1722例健康对照。我们发现了20个新的变异携带者，加上之前发现的8个，发病年龄比非携带者年轻（分别为51.0±10.7岁对58.3±11.0岁）；P = 0.01)。所有携带者对多巴胺能治疗和器械辅助治疗均有良好的反应。携带者有轻度或无认知能力下降，有轻度或无抑郁症状；6人有冲动控制障碍，1人有快速眼动行为障碍。55.5%的患者家族史为阳性，而无变异的患者为22.0% (P <；0.001)，符合显性遗传模式。该变异未在非典型帕金森患者中发现。结论本研究证实RAB32与相对年轻成人发病的PD相关，并具有良好的治疗反应。这种变异应该包括在用于诊断家族性和/或相对年轻发病PD的遗传面板中。©2024作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.