BackgroundThe p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD).ObjectiveThe aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD.MethodsWe 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.Resultsp.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.ConclusionsThe 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.

中文翻译：

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RAB32 相关帕金森病的遗传学和流行病学见解


背景p.Ser71Arg RAB32 变体最近与帕金森病 （PD） 相关。目的目的是调查 RAB32 变异在受 PD 影响和未受 PD 影响的大型多种族个体群体中存在。方法我们查询了我们的专有数据库，其中包含 >180,000 个个体的外显子组/基因组测序数据。对其他 PD 患者进行基因分型，并构建近端 p.Ser71Arg 相关单倍型。结果p.Ser71Arg 存在于 11 名 PD 患者 （73% 来自意大利北部） 和 35 名年龄 <50 岁无 PD 相关症状的个体 （89% 来自中东和北非 [MENA]）。它是在一组近端单核苷酸多态性中发现的。其他 RAB32 变异在 PD 和非 PD 个体中相当频繁。结论RAB32 p.Ser71Arg 变体定义了意大利北部的一组 PD 患者。在全球范围内，它在中东和北非地区最为普遍。我们的数据表明，p.Ser71Arg 会导致 PD，并且它只通过创始人事件发生过一次。其他 RAB32 变体不太可能导致 PD。© 2024 作者。由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版的《运动障碍》。