关于 RAB32 相关帕金森病的遗传学和流行病学见解

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-10-26 DOI:10.1002/mds.30041

Mandy Radefeldt, Sabrina Lemke, Kridsadakorn Chaichoompu, Jefri Jeya Paul, Filipa Curado, Franco Valzania, Francesco Cavallieri, Valentina Fioravanti, Enza Maria Valente, Micol Avenali, Anna Negrotti, Hasmet A. Hanagasi, Sven Thonke, Michele Matarazzo, Andrea Panzavolta, Chiara Cerami, Ana Westenberger, Christine Klein, Peter Bauer, Christian Beetz

{"title":"关于 RAB32 相关帕金森病的遗传学和流行病学见解","authors":"Mandy Radefeldt, Sabrina Lemke, Kridsadakorn Chaichoompu, Jefri Jeya Paul, Filipa Curado, Franco Valzania, Francesco Cavallieri, Valentina Fioravanti, Enza Maria Valente, Micol Avenali, Anna Negrotti, Hasmet A. Hanagasi, Sven Thonke, Michele Matarazzo, Andrea Panzavolta, Chiara Cerami, Ana Westenberger, Christine Klein, Peter Bauer, Christian Beetz","doi":"10.1002/mds.30041","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"18 1","pages":""},"PeriodicalIF":7.4000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic and Epidemiological Insights into RAB32‐Linked Parkinson's Disease\",\"authors\":\"Mandy Radefeldt, Sabrina Lemke, Kridsadakorn Chaichoompu, Jefri Jeya Paul, Filipa Curado, Franco Valzania, Francesco Cavallieri, Valentina Fioravanti, Enza Maria Valente, Micol Avenali, Anna Negrotti, Hasmet A. Hanagasi, Sven Thonke, Michele Matarazzo, Andrea Panzavolta, Chiara Cerami, Ana Westenberger, Christine Klein, Peter Bauer, Christian Beetz\",\"doi\":\"10.1002/mds.30041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":213,\"journal\":{\"name\":\"Movement Disorders\",\"volume\":\"18 1\",\"pages\":\"\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2024-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Movement Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/mds.30041\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Movement Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mds.30041","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景最近发现p.Ser71Arg RAB32变体与帕金森病（PD）有关。方法我们查询了我们的专有数据库，该数据库包含18万人的外显子组/基因组测序数据。结果p.Ser71Arg存在于11名帕金森病患者（73%来自意大利北部）和35名年龄在50岁以下、无帕金森病相关症状的个体（89%来自中东和北非[MENA]）中。在一组近端单核苷酸多态性中发现了顺式变异。结论 RAB32 p.Ser71Arg 变异定义了意大利北部的一个帕金森病患者群。在全球范围内，它在中东和北非地区最为流行。我们的数据表明，p.Ser71Arg 会导致帕金森病，而且它只发生过一次，是通过一个创始事件发生的。其他 RAB32 变体不太可能导致帕金森病。© 2024 作者。运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Genetic and Epidemiological Insights into RAB32‐Linked Parkinson's Disease

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.