{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:40:22Z","timestamp":1785804022690,"version":"3.56.0"},"reference-count":24,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"unspecified","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Akureyri Hospital Research Fund"},{"name":"The Icelandic Cardiac Society Research Fund"},{"name":"Landspitali\u2013The National University Hospital of Iceland Research Fund"},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1P20HL101408"],"award-info":[{"award-number":["1P20HL101408"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1P50HL112349"],"award-info":[{"award-number":["1P50HL112349"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["5HL084553"],"award-info":[{"award-number":["5HL084553"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2020,2,12]]},"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The myosin-binding protein C (<jats:italic>MYBPC3<\/jats:italic>) c.927-2A&gt;G founder mutation accounts for &gt;90% of sarcomeric hypertrophic cardiomyopathy (HCM) in Iceland. This cross-sectional observational study explored the penetrance and phenotypic burden among carriers of this single, prevalent founder mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied 60 probands with HCM caused by <jats:italic>MYBPC3<\/jats:italic> c.927-2A&gt;G\u2009and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Genetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+\/LVH+), 59 G+without\u2009LVH (G+\/LVH\u2212) and 117 genotype-negative relatives (unaffected). Compared with HCM probands, G+\/LVH+ relatives were older at HCM diagnosis, had less LVH, a less prevalent diastolic dysfunction, fewer ECG abnormalities, lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I levels, and fewer symptoms. The penetrance of HCM was influenced by age and sex; specifically, LVH was present in 39% of G+males\u2009but only 9% of G+females under age 40 years (p=0.015), versus 86% and 83%, respectively, after age 60 (p=0.89). G+\/LVH\u2212 subjects had normal wall thicknesses, diastolic function and NT-proBNP levels, but subtle changes in LV geometry and more ECG abnormalities than their unaffected relatives.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Phenotypic expression of the Icelandic <jats:italic>MYBPC3<\/jats:italic> founder mutation varies by age, sex and proband status. Men are more likely to have LVH at a younger age, and disease manifestations were more prominent in probands than in relatives identified via family screening. G+\/LVH\u2212 individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2019-001220","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T05:05:15Z","timestamp":1586149515000},"page":"e001220","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Hypertrophic cardiomyopathy in myosin-binding protein C (<i>MYBPC3<\/i>) Icelandic founder mutation carriers"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-0963","authenticated-orcid":false,"given":"Berglind","family":"Adalsteinsdottir","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Iceland, Reykjavik, Iceland"},{"name":"Division of Cardiology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Cardiology Division, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J","family":"Maron","sequence":"additional","affiliation":[{"name":"Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnar","family":"Danielsen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Lopez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain"},{"name":"Carlos III Health Institute, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Diez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Navarra, Spain"},{"name":"Carlos III Health Institute, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Jarolim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Seidman","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn Y","family":"Ho","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar Th","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Iceland, Reykjavik, Iceland"},{"name":"Department of Medicine, Akureyri Hospital, Akureyri, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,4,5]]},"reference":[{"key":"2025081612075332000_7.1.e001220.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102923"},{"key":"2025081612075332000_7.1.e001220.2","doi-asserted-by":"crossref","unstructured":"van Velzen HG , Schinkel AFL , Oldenburg RA , et al . 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