{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:13:24Z","timestamp":1792761204453,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2014,9,30]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>The geographic isolation and homogeneous population of Iceland are ideally suited to ascertain clinical and genetic characteristics of hypertrophic cardiomyopathy (HCM) at the population level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Medical records and cardiac imaging studies obtained between 1997 and 2010 were reviewed to identify Icelandic patients with HCM. Surviving patients were recruited for clinical and genetic studies. A previously identified Icelandic mutation,\n              <jats:italic>MYBPC3<\/jats:italic>\n              c.927-2A&gt;G, was genotyped, and mutation-negative samples were sequenced for HCM genes and other hypertrophic genes. Record review identified 180 patients with HCM. Genetic analyses of 151 patients defined pathogenic mutations in 101 (67%), including\n              <jats:italic>MYBPC3<\/jats:italic>\n              c.927-2A&gt;G (88 patients, 58%), 4 other\n              <jats:italic>MYBPC3<\/jats:italic>\n              or\n              <jats:italic>MYH7<\/jats:italic>\n              mutations (5 patients, 3.3%), and 2\n              <jats:italic>GLA<\/jats:italic>\n              mutations (8 patients, 5.3%). Haplotype and genetic genealogical data defined\n              <jats:italic>MYBPC3<\/jats:italic>\n              c.927-2A&gt;G as a founder mutation, introduced into the Icelandic population in the 15th century, with a current population prevalence of 0.36%.\n              <jats:italic>MYBPC3<\/jats:italic>\n              c.927-2A&gt;G mutation carriers exhibited phenotypic diversity but were younger at diagnosis (42 versus 49 years;\n              <jats:italic>P<\/jats:italic>\n              =0.001) and sustained more adverse events (15% versus 2%;\n              <jats:italic>P<\/jats:italic>\n              =0.02) than mutation-negative patients. All-cause mortality for patients with HCM was similar to that of an age-matched Icelandic population (hazard ratio, 0.98;\n              <jats:italic>P<\/jats:italic>\n              =0.9). HCM-related mortality (0.78%\/y) occurred at a mean age of 68 compared with 81 years for non\u2013HCM-related mortality (\n              <jats:italic>P<\/jats:italic>\n              =0.02).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              A founder\n              <jats:italic>MYBPC3<\/jats:italic>\n              mutation that arose &gt;550 years ago is the predominant cause of HCM in Iceland. The\n              <jats:italic>MYBPC3<\/jats:italic>\n              c.927-2A&gt;G mutation is associated with low adverse event rates but earlier cardiovascular mortality, illustrating the impact of genotype on outcomes in HCM.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.114.011207","type":"journal-article","created":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T08:15:25Z","timestamp":1406794525000},"page":"1158-1167","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["Nationwide Study on Hypertrophic Cardiomyopathy in Iceland"],"prefix":"10.1161","volume":"130","author":[{"given":"Berglind","family":"Adalsteinsdottir","sequence":"first","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polakit","family":"Teekakirikul","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Maron","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Burke","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Gudbjartsson","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilma","family":"Holm","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Stefansson","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"DePalma","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Mazaika","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"McDonough","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnar","family":"Danielsen","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); Cardiovascular Division, Brigham and Women\u2019s Hospital,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar T.","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"From Landspitali\u2013The National University Hospital of Iceland, Reykjavik, Iceland (B.A., R.D.); Faculty of Medicine (B.A., K.S., G.T.G.) and School of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., S.R.D., E.M., B.M., J.G.S., C.E.S.); Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (B.J.M.); 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