[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-456519-105":59,"doc-detail-456519-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","rab3a-variants-in-ataxia-and-other-neurodegenerative-disorders","RAB3A variants in ataxia and other neurodegenerative disorders","","Letter response discussing RAB3A monoallelic variants as a genetic cause of autosomal dominant cerebellar ataxia and their expansion to related phenotypes. The authors reference prior reports describing recurrent variants (notably p.Arg83Trp) across cerebellar ataxia families and additional de novo/nonsense variants in neurodevelopmental disorders. Their own screening of unsolved Italian cases finds four heterozygous RAB3A variants in ataxia and Parkinson’s disease cohorts, with segregation and neuroimaging observations, and no detection in healthy controls.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/rab3a-variants-in-ataxia-and-other-neurodegenerative-disorders/456519/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/rab3a-variants-in-ataxia-and-other-neurodegenerative-disorders/456519.png","ImageObject",300,407,{"name":92,"@type":93},"jayni","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which RAB3A variants were highlighted as recurrent or functionally notable in prior reports?","Question",{"text":112,"@type":113},"Prior reports described a recurrent p.Arg83Trp variant across multiple autosomal dominant cerebellar ataxia families, along with additional de novo or nonsense RAB3A variants in neurodevelopmental disorder families.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the authors screen for RAB3A variants and which patient groups were included?",{"text":117,"@type":113},"They screened their in-house whole-exome/whole-genome sequencing datasets of unsolved Italian index cases covering cerebellar ataxia, spastic ataxia, and spastic paraplegia, and they extended the search to Parkinson’s disease patients and an unrelated healthy Italian control dataset.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key results regarding frequency and presence in controls?",{"text":121,"@type":113},"Four heterozygous RAB3A variants were found in five unrelated patients, with reported detection rates in ataxia and Parkinson’s disease cohorts, and none of the identified variants were detected in the healthy control dataset.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},456519,1791165597,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":39,"preview_page_count":4},3985747859343,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","[https://doi.org/10.1093/brain/awaf383](https://doi.org/10.1093/brain/awaf383) BRAIN 2026: 149; e1–e3 | e1  \nRAB3A variants in ataxia and other neurodegenerative disorders  \nMarco Percetti,1,2 Edoardo Monfrini,2 Roberto Del Bo,1 Margherita Canesi,3 Francesco Cavallieri,4 Giulia Di Rauso,4,5 Valentina Fioravanti,4 Eleonora Del Prete,6 Daniela Frosini,6 Giovanni Palermo,6,7 Roberto Ceravolo,6,7 Giorgio Sacilotto8 and Alessio Di Fonzo2  \n1 Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy  \n2 Neurology Unit, Department of Neuroscience and Mental Health, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy  \n3 Department of Neurological Rehabilitation, Parkinson’s Disease and Movement Disorders Center, Moriggia-Pelascini Hospital, Gravedona ed Uniti 22015, Italy  \n4 Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia 42122, Italy  \n5 Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena 42121, Italy  \n6 Center for Neurodegenerative Diseases, Parkinson’s Disease and Movement Disorders Unit of Neurology, Department of Neuroscience, University of Pisa, Santa Chiara Hospital, Pisa 56126, Italy  \n7 Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy  \n8 Parkinson Institute, ASST G.Pini-CTO, Milan 20122, Italy  \nCorrespondence to: Dr Alessio Di Fonzo  \nNeurology Unit, Department of Neuroscience and Mental Health, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan 20122, Italy  \nE-mail: [alessio.difonzo@policlinico.mi.it](alessio.difonzo@policlinico.mi.it)  \nWe read with great interest the recent article by Hengel and colleagues1 in Brain, reporting monoallelic variantsintheRAB3A gene as a novel cause of autosomal dominant cerebellar ataxia.  \nThe authors reported 18 patients with cerebellar ataxia from 10 unrelated families, each carrying a rare heterozygous RAB3A variant. Notably, the p.Arg83Trp variant recurred in nine families. Affected carriers predominantly presented with adult-onset, isolated cerebellar ataxia. Furthermore, three unrelated families with neurodevelopmental disorders were found to carry de novo or nonsense RAB3A variants.  \nThereafter, Mouraux and colleagues2 screened RAB3A in a cohort of 1235 individuals with cerebellar ataxia and/or spastic paraplegia who underwent whole exome sequencing (WES) . They identified 10 heterozygous carriers from five unrelated families. The p.Arg83Trp variant recurred in three families with autosomal  \ndominant cerebellar ataxia. The p.Arg41Cys variant was identified in two siblings with dominant spastic paraplegia, whereas thep.Asp181Tyr was detected in one patient with spastic paraplegia and parkinsonism.  \nPrompted by these findings, we screened for RAB3A variants in our in-house WES and whole genome sequencing dataset of unsolved index cases from Italy with cerebellarataxia (n = 116), spastic ataxia (n = 15), and spastic paraplegia (n = 27) . Owing to the observation of parkinsonism in a RAB3A affected carrier, we also searched for RAB3A variants in patients with Parkinson’s disease (PD) (n = 958)(Supplementary Table 2) . The search was extended to a control dataset of 1686 unrelated healthy Italians (Network for Italian Genomes—Exomes from ITaly, freely available online at [http://](http://)[ ](http://)[nigdb.ext.cineca.it/](nigdb.ext.cineca.it/)).  \nReceived September 22, 2025. Accepted September 30, 2025. Advance access publication October 15, 2025 © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ([https://creativecommons.org/licenses/by](https://creativecommons.org/licenses/by)nc/4.0/), which permits non-commercial re-use, distribution, a","cbCaifbQajArEDCM","https://ap.wps.com/l/cbCaifbQajArEDCM","pdf",371707,"English","# Letter context and prior findings\n## Screening approach and cohorts\n# Identified variants and clinical correlations\n## Variant-specific observations and controls","[{\"question\":\"Which RAB3A variants were highlighted as recurrent or functionally notable in prior reports?\",\"answer\":\"Prior reports described a recurrent p.Arg83Trp variant across multiple autosomal dominant cerebellar ataxia families, along with additional de novo or nonsense RAB3A variants in neurodevelopmental disorder families.\"},{\"question\":\"How did the authors screen for RAB3A variants and which patient groups were included?\",\"answer\":\"They screened their in-house whole-exome/whole-genome sequencing datasets of unsolved Italian index cases covering cerebellar ataxia, spastic ataxia, and spastic paraplegia, and they extended the search to Parkinson’s disease patients and an unrelated healthy Italian control dataset.\"},{\"question\":\"What were the key results regarding frequency and presence in controls?\",\"answer\":\"Four heterozygous RAB3A variants were found in five unrelated patients, with reported detection rates in ataxia and Parkinson’s disease cohorts, and none of the identified variants were detected in the healthy control dataset.\"}]","RAB3A variants in ataxia and other neurodegenerative disorders | PDF",1790746294]