{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:13:31Z","timestamp":1789654411054,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Transthyretin hereditary amyloidosis (ATTRv) clinical variability has been widely reported, not only across countries and variants but also among families and distinct regions within a single nation. One of the principal challenges in disease management is the accurate determination of age of onset (AOO), which is heterogeneous and has therapeutic implications given the availability of disease\u2010modifying treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study characterizes the genetic landscape and clinical onset spectrum of ATTRv in an admixed Brazilian cohort of 175 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven\n                      <jats:italic>TTR<\/jats:italic>\n                      pathogenic variants (p.Val50Met, p.Val142Ile, p.Ile127Val, p.Ile88Leu, p.Ala39Asp, p.Phe84Leu, p.Tyr98Phe) were identified. The most common was p.Val50Met (58.8%), followed by p.Val142Ile (29.7%) and p.Ile127Val (7.4%). Notably, 44% of V122I had a neurological onset. Close clinical monitoring of presymptomatic carriers reduced age at diagnosis by 10.5\u2009years. The median AOO was 50\u2009years, with V30M patients presenting earlier (38.5\u2009years) than V122I (p.Val142Ile) (60y) and I107V (p.Ile127Val) (60\u2009years). Familial cases showed a 20.5\u2010year earlier AOO than sporadic cases. In Brazil, late\u2010onset (&gt;\u200950\u2009years) V30M is more common than previously reported (37.5%); ethnicity can influence AOO within the same variant, and for the first time, we show a distinct geographic pattern: early\u2010onset V30M is more frequent in S\u00e3o Paulo\/South, whereas late\u2010onset V30M predominates in the central region.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This study emphasizes the heterogeneity of ATTRv presentation in admixed populations and underscores the need for expanded screening and multicenter studies to refine genotype\u2013phenotypic correlations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jns.70097","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:57:26Z","timestamp":1767797846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic and Clinical Spectrum of Hereditary Transthyretin Amyloidosis in Brazil"],"prefix":"10.1111","volume":"31","author":[{"given":"Gustavo","family":"Maximiano\u2010Alves","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Lavigne\u2010Moreira","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vinicius","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Internal Medicine, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adilson Junior Pinto","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Multidisciplinary Center for Amyloidosis\/Neurocop\u2014Irece  Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio Henrique","family":"Valicelli","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Internal Medicine, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Saraiva","family":"Coneglian","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Internal Medicine, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-6831","authenticated-orcid":false,"given":"Elisa","family":"Vegezzi","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Manoel Marques","family":"Garibaldi","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Jos\u00e9","family":"Tomaselli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Behavioral Sciences, Ribeir\u00e3o 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