{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T07:19:13Z","timestamp":1784618353620,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","award":["16880"],"award-info":[{"award-number":["16880"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (TTR) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic spectrum of hATTR in Austria. Methods: Within the period of 2014\u20132019, patients with ATTR-associated cardiomyopathy and\/or unexplained progressive polyneuropathies were screened for mutations in the TTR gene. Results: We identified 43 cases from 22 families carrying 10 different TTR missense mutations and confirmed two mutational hot spots at c.323A&gt;G (p.His108Arg) and c.337G&gt;C (p.Val113Leu). Two further patients with late onset ATTR carried TTR variants of unknown significance. The majority of patients initially presented with heart failure symptoms that were subsequently accompanied by progressive polyneuropathy in most cases. A total of 55% had a history of carpal tunnel syndrome before the onset of other organ manifestations. Conclusions: Our study underlined the relevance of hATTR in the pathogenesis of amyloid-driven cardiomyopathy and axonal polyneuropathy and indicated considerable genetic heterogeneity of this disease in the Austrian population. The estimated prevalence of hATTR in Austria based on this study is 1:200,000 but a potentially higher number of unknown cases must be taken into account. With respect to new therapeutic approaches, we strongly propose genetic testing of the TTR gene in an extended cohort of patients with unexplained heart failure and progressive polyneuropathy.<\/jats:p>","DOI":"10.3390\/jcm9072234","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T11:03:23Z","timestamp":1594724603000},"page":"2234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots"],"prefix":"10.3390","volume":"9","author":[{"given":"Michaela","family":"Auer-Grumbach","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Rettl","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Ablasser","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermine","family":"Agis","sequence":"additional","affiliation":[{"name":"Department of Hematology &amp; Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7061-2895","authenticated-orcid":false,"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"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":"Martin","family":"Gattermeier","sequence":"additional","affiliation":[{"name":"Landesklinikum Waidhofen\/Ybbs, 3340 Waidhofen an der Ybbs, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Krems, 3500 Krems, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hacker","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-543X","authenticated-orcid":false,"given":"Renate","family":"Kain","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Krems, 3500 Krems, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"Gabor G.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology and Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 0S8, Canada"},{"name":"Institute of Neurology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lampl","sequence":"additional","affiliation":[{"name":"Department of Neurology, Konventhospital der Barmherzigen Br\u00fcder Linz, 4021 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neira","family":"Ljevakovic","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Nagele","sequence":"additional","affiliation":[{"name":"Office for Internal Medicine, Spittal\/Drau, 9800 Spittal an der Drau, Carinthia, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2588-6739","authenticated-orcid":false,"given":"Gerhard","family":"P\u00f6lzl","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Quasthoff","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Raimann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Krems, 3500 Krems, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Rauschka","sequence":"additional","affiliation":[{"name":"Department of Neurology, SMZ-Ost Hospital, 1220 Vienna, Austria"},{"name":"Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders\/SMZ-Ost Hospital, 1220 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5155-4017","authenticated-orcid":false,"given":"Christian","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kepler University Hospital, Medical Faculty, Johannes Kepler University, 4040 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volha","family":"Skrahina","sequence":"additional","affiliation":[{"name":"Centogene AG, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Othmar","family":"Schuhfried","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, 1090 Vienna, 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"}]},{"given":"Nicolas D.","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wanschitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II (Cardiology, Intensive Care Medicine), Klinikum Wels-Grieskirchen, 4600 Wels, 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":"Raphael","family":"Wurm","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/WCO.0000000000000476","article-title":"Familial amyloid polyneuropathy","volume":"30","author":"Adams","year":"2017","journal-title":"Curr. 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