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Around 10% of ALS is familial, and in Brazilian families the VAPB gene P56S pathogenic variant is a notable driver of the rare ALS8 subtype with distinct, slower progression. This study screens Brazilian FALS patients to identify VAPB pathogenic variants and characterize the associated clinical presentation and disease course. Clinical, laboratory, and electrophysiological review with VAPB sequencing was applied to 12 families.",{"@graph":69,"@context":123},[70,84,106],{"@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/genetic-and-clinical-insights-into-als8-exploring-the-impact-of-vapb-pathogenic-variants-in-familial-amyotrophic-lateral-sclerosis/435967/",{"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/genetic-and-clinical-insights-into-als8-exploring-the-impact-of-vapb-pathogenic-variants-in-familial-amyotrophic-lateral-sclerosis/435967.png","ImageObject",300,407,{"name":92,"@type":93},"Emma Wilson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is ALS8 and why is VAPB important in familial ALS?","Question",{"text":113,"@type":114},"ALS8 is a rare familial ALS subtype associated with pathogenic variants in the VAPB gene, particularly the P56S variant, which shows distinct clinical features and slower progression than typical ALS.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What was the main objective of the study?",{"text":118,"@type":114},"To identify VAPB gene pathogenic variants in Brazilian FALS patients, with a focus on the P56S variant linked to ALS8, and to explore its clinical presentation and progression.",{"name":120,"@type":111,"acceptedAnswer":121},"How were patients selected and VAPB variants identified?",{"text":122,"@type":114},"Twelve FALS patients from 12 unrelated families in Rio de Janeiro were included between 2023 and 2024. Clinical, laboratory, and electrophysiological data were reviewed, DNA was collected via oral swabs, and VAPB sequencing was performed to detect pathogenic variants.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},435967,1790779556,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Article published online: 2025-11-04  \nOriginal Article 1  \nGenetic and clinical insights into ALS8: exploring the impact of VAPB pathogenic variants in familial amyotrophic lateral sclerosis  \nAdriana Helena de Oliveira Reis 1 Gabriella Pereira de Oliveira Magno 1 Bruna Guimarães de França Costa 1 Luna Borges Figalo 1 Marco Orsini2,3  \n1 Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcântara Gomes, Departamento de Genética, Rio de Janeiro RJ, Brazil.  \n2 Universidade Iguaçu, Faculdade de Medicina, Programa de Pós-Graduação em Vigilância em Saúde, Nova Iguaçu RJ, Brazil.  \n3 Universidade Federal do Rio de Janeiro, Instituto de Psiquiatria, Rio de Janeiro RJ, Brazil.  \nArq. Neuro-Psiquiatr. 2025;83(11):s00451812470 .  \nAddress for correspondence Adriana Helena de Oliveira Reis (email: [adriana.helena@uerj.br](adriana.helena@uerj.br))  \nAbstract  \nKeywords  \n► Neurodegenerative Diseases  \n► Motor Neurons  \n► Genetic Variation  \n► Muscle Weakness  \nBackground Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to progressive muscle weakness and paralysis. Approximately 10% of ALS cases are familial (FALS), with the VAPB gene’s P56S pathogenic variant being notably prevalent in Brazilian families, contributing to the rare ALS8 . This variant progresses more slowly than typical ALS, with distinct clinical features.  \nObjective To identify VAPB gene pathogenic variants in Brazilian FALS patients, particularly the P56S pathogenic variant associated with ALS8 and explore its clinical presentation and progression.  \nMethods Twelve FALS patients from 12 unrelated families in Rio de Janeiro were included in the study between 2023 and 2024 . Clinical, laboratory, and electrophysiological data were reviewed. Collection of DNA samples happened via oral swabs, and VAPB gene sequencing was performed to identify pathogenic variants, specifically the P56S variant linked to ALS8 .  \nResults There were 3 cases of the P56S pathogenic variant, all presenting ALS8 with symptom onset in the lower limbs and slower disease progression. A family with 11 affected members across four generations showed an autosomal dominant inheritance pattern, with varying survival rates, highlighting its clinical variability.  \nConclusion The present study underscores the importance of genetic screening for ALS subtypes, particularly ALS8, in Brazil. Identifying the P56S pathogenic variant enhances our understanding of ALS’s genetic diversity and clinical presentation, offering a foundation for improved diagnostic practices and personalized care.  \nreceived  \nNovember 28, 2024 received in its final form July 9, 2025  \naccepted  \nAugust 16, 2025  \nDOI [https://doi.org/](https://doi.org/)[ ](https://doi.org/)10.1055/s-0045-1812470 . ISSN 0004-282X.  \nEditor-in-Chief: Hélio A. G. Teive.  \nAssociate Editor: Wilson Marques Jr.  \n© 2025 . The Author(s) .  \nThis is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/))  \nThieme Revinter Publicações Ltda. , Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil  \n2 Impact of VAPB pathogenic variants in FALS cases Reis et al.  \nINTRODUCTION  \nAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscular atrophy and the simultaneous degeneration of lower (spinal and bulbar) and upper (corticospinal) motor neurons leading to muscle weakness, fasciculation, speech and swallowing disabilities, and progressive paralysis. Survival rate in most patients is 2 to 5 years.1  \nApproximately 10% of ALS cases are familiar (FALS) and 90% are sporadic (SALS).2 Except for some familial cases with clearly distinct features, the majority of ALS cases are clinically indistinguishable","cbCaigYjF5aR7HNO","https://ap.wps.com/l/cbCaigYjF5aR7HNO","pdf",632792,"English","# Abstract\n## Background\n## Objective\n## Methods\n## Results\n## Conclusion\n# Introduction\n## Disease overview and survival\n## Familial vs sporadic ALS\n## Genetics of ALS and Brazil\n# Methods","[{\"question\":\"What is ALS8 and why is VAPB important in familial ALS?\",\"answer\":\"ALS8 is a rare familial ALS subtype associated with pathogenic variants in the VAPB gene, particularly the P56S variant, which shows distinct clinical features and slower progression than typical ALS.\"},{\"question\":\"What was the main objective of the study?\",\"answer\":\"To identify VAPB gene pathogenic variants in Brazilian FALS patients, with a focus on the P56S variant linked to ALS8, and to explore its clinical presentation and progression.\"},{\"question\":\"How were patients selected and VAPB variants identified?\",\"answer\":\"Twelve FALS patients from 12 unrelated families in Rio de Janeiro were included between 2023 and 2024. Clinical, laboratory, and electrophysiological data were reviewed, DNA was collected via oral swabs, and VAPB sequencing was performed to detect pathogenic variants.\"}]","Genetic and clinical insights into ALS8 - exploring the impact of VAPB pathogenic variants in familial amyotrophic lateral sclerosis | PDF",1790676156,13]