A Nationwide Study on Hypertrophic Cardiomyopathy in Iceland: Evidence of a MYBPC3 Founder Mutation.

• Published in: Circulation
• Main Authors: Adalsteinsdottir, Berglind, Teekakirikul, Polakit, Maron, Barry J, Burke, Michael A, Gudbjartsson, Daniel F, Holm, Hilma, Stefansson, Kari, DePalma, Steven R, Mazaika, Erica, McDonough, Barbara, Danielsen, Ragnar, Seidman, Jonathan G, Seidman, Christine E, Gunnarsson, Gunnar Th
• Other Authors: 1Landspitali, The National University Hospital of Iceland, Reykjavik; University of Iceland, Reykjavik, Iceland [e-mail]. 2Harvard Medical School, Boston, MA. 3Minneapolis Heart Institute Foundation, Minneapolis, MN. 4Harvard Medical School; Brigham and Women's Hospital, Boston, MA. 5deCODE Genetics, Reykjavik; University of Iceland, Reykjavik, Iceland. 6deCODE Genetics, Reykjavik, Iceland. 7University of Iceland, Reykjavik; deCODE Genetics, Reykjavik, Iceland. 8Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. 9Harvard Medical School; Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA. 10University of Iceland, Reykjavik; Akureyri Hospital, Akureyri, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Lippincott Williams & Wilkins 2014
• Subjects: Hjartasjúkdómar; Arfgengi; Cardiomyopathy; Hypertrophic/mortality*; Hypertrophic/genetics*; Carrier Proteins/genetics*; Iceland/epidemiology; Genetic Predisposition to Disease/genetics*; Genetic Predisposition to Disease/epidemiology*; Adolescent; Adult; Age of Onset; Aged; 80 and over; Child; Preschool; Female; Founder Effect*; Haplotypes; Humans; Male; Middle Aged; Phenotype; Prevalence; Young Adult; Akureyri; Iceland
• Online Access: http://hdl.handle.net/2336/325615; https://doi.org/10.1161/CIRCULATIONAHA.114.011207

To access publisher's full text version of this article click on the hyperlink at the bottom of the page -The geographic isolation and homogeneous population of Iceland is ideally suited to ascertain clinical and genetic characteristics of hypertrophic cardiomyopathy (HCM) at the population level. -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, MYBPC3 c.927-2A>G, was genotyped, and mutation-negative samples were sequenced for HCM genes and other hypertrophic genes. Record review identified 180 HCM patients. Genetic analyses of 151 patients defined pathogenic mutations in 101 (67%), including MYBPC3 c.927-2A>G (88 patients; 58%), 4 other MYBPC3 or MYH7 mutations (5 patients; 3.3%), and 2 GLA mutations (8 patients; 5.3%). Haplotype and genetic genealogical data defined MYBPC3 c.927-2A>G as a founder mutation, introduced into the Icelandic population in the 15(th) century, with a current population prevalence of 0.36%. MYBPC3 c.927-2A>G mutation carriers exhibited phenotypic diversity but were younger at diagnosis (42 vs. 49 years, p=0.001) and sustained more adverse events (15% vs. 2%, p=0.02) than mutation-negative patients. All-cause mortality for HCM patients was similar to an age-matched Icelandic population (Hazard Ratio 0.98, p=0.9). HCM-related mortality (0.78%/year) occurred at a mean age of 68 compared to 81 years for non-HCM related mortality (p=0.02). -A founder MYBPC3 mutation that arose over 550 years ago is the predominant cause of HCM in Iceland. The MYBPC3 c.927-2A>G mutation is associated with low adverse event rates but earlier cardiovascular mortality, illustrating the impact of genotype on outcomes in HCM. Akureyri Hospital Research Fund (G.G.), Landspitali – The National University Hospital of Iceland (Research Fund project A-2013-011; B.A.), the National Institutes of Health ...