{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:22:46Z","timestamp":1762302166206,"version":"build-2065373602"},"reference-count":25,"publisher":"Georg Thieme Verlag KG","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq Neuropsiquiatr"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1055\/s-0045-1812470","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:18:35Z","timestamp":1762301915000},"page":"001-005","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and clinical insights into ALS8: exploring the impact of VAPB pathogenic variants in familial amyotrophic lateral sclerosis"],"prefix":"10.1055","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7458-131X","authenticated-orcid":false,"given":"Adriana Helena de Oliveira","family":"Reis","sequence":"additional","affiliation":[{"name":"Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alc\u00e2ntara Gomes, Departamento de Gen\u00e9tica, Rio de Janeiro RJ, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2961-8138","authenticated-orcid":false,"given":"Gabriella Pereira de Oliveira","family":"Magno","sequence":"additional","affiliation":[{"name":"Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alc\u00e2ntara Gomes, Departamento de Gen\u00e9tica, Rio de Janeiro RJ, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1336-1781","authenticated-orcid":false,"given":"Bruna Guimar\u00e3es de Fran\u00e7a","family":"Costa","sequence":"additional","affiliation":[{"name":"Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alc\u00e2ntara Gomes, Departamento de Gen\u00e9tica, Rio de Janeiro RJ, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7017-5880","authenticated-orcid":false,"given":"Luna Borges","family":"Figalo","sequence":"additional","affiliation":[{"name":"Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alc\u00e2ntara Gomes, Departamento de Gen\u00e9tica, Rio de Janeiro RJ, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-6937","authenticated-orcid":false,"given":"Marco","family":"Orsini","sequence":"additional","affiliation":[{"name":"Universidade Igua\u00e7u, Faculdade de Medicina, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Vigil\u00e2ncia em Sa\u00fade, Nova Igua\u00e7u RJ, Brazil."},{"name":"Universidade Federal do Rio de Janeiro, Instituto de Psiquiatria, Rio de Janeiro RJ, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1750-1326-8-28","article-title":"Genetics of amyotrophic lateral sclerosis: an 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