{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:22Z","timestamp":1787014162095,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The F64L variant is among the most frequent TTR mutations in Italy, typically associated with a predominantly neurologic phenotype and limited cardiac involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from 181 ATTRv patients in the multicenter Patisiranitaly database treated with Patisiran since 2020 were analyzed. Neurologic impairment scores, Norfolk QoL\u2010DN, and cardiac parameters were compared between F64L (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200956), V30M (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200937), and non\u2010F64L (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009125) patients at baseline and during follow\u2010up. Cluster analysis was applied to identify patient subgroups based on these variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>F64L represented 30.9% of the cohort. Compared to non\u2010F64L patients, F64L patients had a higher prevalence of neurologic onset and neurologic phenotype, a thinner interventricular septum, and lower NT\u2010proBNP levels. Cluster analysis segregated patients into two distinct groups, predominantly reflecting F64L vs. non\u2010F64L status and corresponding neurologic severity. F64L patients showed milder cardiac involvement compared to V30M patients. Longitudinal repeated\u2010measures ANOVA showed stable clinical and instrumental measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>F64L is characterized by predominant neurologic involvement and milder cardiac involvement in this Patisiran\u2010treated cohort. Mutation\u2010specific diagnostic and follow\u2010up strategies are essential to capture its natural history and treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70657","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:55:48Z","timestamp":1780379748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep Phenotyping of\n                    <scp>F64L<\/scp>\n                    Mutation in a Multicentric Cohort of Patisiran\u2010Treated Hereditary Transthyretin Amyloidosis Patients (Patisiranitaly)"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8897-3736","authenticated-orcid":false,"given":"Marco","family":"Ceccanti","sequence":"first","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Guaraldi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche Di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-1509","authenticated-orcid":false,"given":"Angela","family":"Romano","sequence":"additional","affiliation":[{"name":"Dipartimento Di Neuroscienze, Organi Di Senso E Torace, UOC Neurologia Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Antonini","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology Sapienza University of Rome and UniCamillus\u2010Saint Camillus International University of Health Sciences  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Barilaro","sequence":"additional","affiliation":[{"name":"AOU Careggi and Department of Neurosciences, Drug and Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Briani","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neuroscience University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Burattini","sequence":"additional","affiliation":[{"name":"Neurology Unit Ospedale Santa Croce Di Fano  Fano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Gianoli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche Di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Carlini","sequence":"additional","affiliation":[{"name":"Neurological Clinic, Department of Experimental and Clinical Medicine Marche Polytechnic University  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Cianci","sequence":"additional","affiliation":[{"name":"Neurology Unit Great Metropolitan Hospital \u201cBianchi Melacrino Morelli\u201d  Reggio Calabria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Curr\u00f2","family":"Dossi","sequence":"additional","affiliation":[{"name":"Department of Neurology Infermi Hospital  Rimini Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Di Lisi","sequence":"additional","affiliation":[{"name":"Division of Cardiology University Hospital Paolo Giaccone  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Muzio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences \u201cG. 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