{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:10:11Z","timestamp":1785816611438,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","award":["#62165975"],"award-info":[{"award-number":["#62165975"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Austrian Science Fund","award":["10.55776\/I4699"],"award-info":[{"award-number":["10.55776\/I4699"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a heterogeneous multisystem disease caused by pathogenic transthyretin gene (TTR) variants. Increased awareness and availability of disease-modifying therapies have resulted in increased diagnoses, even in previously nonendemic regions. The aim of this study was to update the nationwide Austrian ATTRv registry by characterizing the clinical, genetic, and regional distribution of TTR variants. Methods: This multicenter, observational analysis examined ATTRv cases diagnosed in Austria between 2014 and 2025. Individuals were included according to the presence of pathogenic or likely pathogenic variants or variants of uncertain significance (VUSs) in TTR. Results: In total, 100 individuals were identified, including symptomatic and asymptomatic carriers. Compared with our previously presented data, the number of genetically confirmed ATTRv cases has more than doubled. Twenty-three TTR variants were identified. The most frequent pathologic variants were p.His108Arg (26%), p.Ile127Phe (11%), and p.Thr69Ile (9%), while p.Val113Leu (9%) represented the most frequent VUS. Significant regional clustering of p.His108Arg was documented in Vienna and Lower Austria. Other findings included a rising number of p.Val142Ile carriers and phenotypically relevant VUSs in 20 patients. Conclusions: Our findings revealed an increasing detection rate of ATTRv in a nonendemic European region. These data underscore the importance of multidisciplinary evaluation, cascade testing, and long-term monitoring to improve early diagnosis and timely management in hereditary amyloidosis.<\/jats:p>","DOI":"10.3390\/jcm15051958","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:11:36Z","timestamp":1772629896000},"page":"1958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hereditary Transthyretin Amyloidosis in Austria: Clinical, Genetic, and Demographic Insights from a Nationwide Cohort"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2744-4233","authenticated-orcid":false,"given":"Nikita","family":"Ermolaev","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang N.","family":"L\u00f6scher","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"P\u00f6lzl","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medial University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Ablasser","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermine","family":"Agis","sequence":"additional","affiliation":[{"name":"Department of Hematology & Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-7910","authenticated-orcid":false,"given":"Christina","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bonderman","sequence":"additional","affiliation":[{"name":"Medical Department 5, Clinic Favoriten, Internal Medicine and Cardiology, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"Cetin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-5274","authenticated-orcid":false,"given":"Franz","family":"Duca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa Antonia","family":"Griedl","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Hacker","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7024-2131","authenticated-orcid":false,"given":"Viktoria","family":"H\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-9879","authenticated-orcid":false,"given":"Andreas","family":"Kammerlander","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-5657","authenticated-orcid":false,"given":"Lukas","family":"Kellermair","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Kepler University Hospital, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera E. A.","family":"Kleinveld","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-3710","authenticated-orcid":false,"given":"Christina","family":"Kronberger","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deddo","family":"M\u00f6rtl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, University Hospital St. P\u00f6lten, 3100 St. P\u00f6lten, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6091-9823","authenticated-orcid":false,"given":"Michael","family":"Poledniczek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical Faculty, Kepler University Hospital, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-5158","authenticated-orcid":false,"given":"Rene","family":"Rettl","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0391-8545","authenticated-orcid":false,"given":"Lena Marie","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-9625","authenticated-orcid":false,"given":"Nora","family":"Schwegel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Schaumberger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Barmherzige Brueder Hospital, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-118X","authenticated-orcid":false,"given":"Raute","family":"Sunder-Plassmann","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2098-9772","authenticated-orcid":false,"given":"Maria","family":"Ungericht","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medial University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-1804","authenticated-orcid":false,"given":"Reinhard","family":"Windhager","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Zimprich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0360-2360","authenticated-orcid":false,"given":"Roza","family":"Badr Eslam","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Auer-Grumbach","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s10072-020-04889-2","article-title":"Hereditary transthyretin amyloidosis overview","volume":"43","author":"Manganelli","year":"2022","journal-title":"Neurol. 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