{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T07:10:26Z","timestamp":1756365026879,"version":"3.44.0"},"reference-count":5,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To report a case of a novel variant of the <jats:italic>TTR<\/jats:italic> gene associated with Cerebral Amyloid Angiopathy (CAA), thereby expanding the spectrum of TTR\u2010related amyloidosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 56\u2010year\u2010old man presented with a history of right fronto\u2010parietal intracerebral haemorrhage and recurrent transient episodes of right arm paraesthesia. Based on clinical and radiological presentation, a probable CAA diagnosis was established according to Boston Criteria 2.0. The patient underwent an extensive evaluation, including genetic testing, cerebrospinal fluid (CSF) analysis and amyloid PET imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CSF analysis and amyloid PET imaging corroborated CAA diagnosis. Genetic testing identified an undescribed heterozygous c.124G &gt; A (p.Gly42Ser) <jats:italic>TTR<\/jats:italic> variant, absent from population databases, within a region known for pathogenic mutations. Family genetic testing revealed the same mutation in the patient's father, who had a history of cerebral haemorrhage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>To our knowledge, this case represents one of the first documented examples of a <jats:italic>TTR<\/jats:italic> gene variant exclusively associated with CAA, in the absence of systemic amyloidosis. These findings suggest the existence of <jats:italic>TTR<\/jats:italic> variants that may result in a brain\u2010restricted amyloid pathology. Genetic screening for <jats:italic>TTR<\/jats:italic> mutations should be considered in familial cases of CAA to refine diagnostic accuracy and guide clinical management strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70217","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:04:33Z","timestamp":1756188273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is a Novel Transthyretin Gene Mutation Associated With Cerebral Amyloid Angiopathy?"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2563-4170","authenticated-orcid":false,"given":"Strazzabosco","family":"Camilla","sequence":"first","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6694-0342","authenticated-orcid":false,"given":"Marinoni","family":"Giulia","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7836-2122","authenticated-orcid":false,"given":"Storti","family":"Benedetta","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balistreri","family":"Francesca","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magri","family":"Stefania","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pollaci","family":"Giuliana","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gorla","family":"Gemma","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-5031","authenticated-orcid":false,"given":"Gatti","family":"Laura","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-628X","authenticated-orcid":false,"given":"Bersano","family":"Anna","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione I.R.C.C.S. Istituto Neurologico \"Carlo Besta\"  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094429"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760\u2010021\u201001854\u20104"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001398"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010015\u20100216\u20100"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.70217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T06:51:50Z","timestamp":1756363910000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.70217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":5,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/ene.70217"],"URL":"https:\/\/doi.org\/10.1111\/ene.70217","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"type":"print","value":"1351-5101"},{"type":"electronic","value":"1468-1331"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70217"}}