Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers
Objective The myosin-binding protein C ( MYBPC3 ) c.927-2A>G founder mutation accounts for >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 mu...
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Online Access: | http://dx.doi.org/10.1136/openhrt-2019-001220 https://syndication.highwire.org/content/doi/10.1136/openhrt-2019-001220 |
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crjcrbmj:10.1136/openhrt-2019-001220 2024-09-30T14:37:33+00:00 Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers Adalsteinsdottir, Berglind Burke, Michael Maron, Barry J Danielsen, Ragnar Lopez, Begoña Diez, Javier Jarolim, Petr Seidman, Jonathan Seidman, Christine E. Ho, Carolyn Y Gunnarsson, Gunnar Th Akureyri Hospital Research Fund The Icelandic Cardiac Society Research Fund Landspitali–The National University Hospital of Iceland Research Fund Howard Hughes Medical Institute Foundation for the National Institutes of Health 2020 http://dx.doi.org/10.1136/openhrt-2019-001220 https://syndication.highwire.org/content/doi/10.1136/openhrt-2019-001220 en eng BMJ https://creativecommons.org/licenses/by/4.0/ Open Heart volume 7, issue 1, page e001220 ISSN 2053-3624 journal-article 2020 crjcrbmj https://doi.org/10.1136/openhrt-2019-001220 2024-09-19T04:13:18Z Objective The myosin-binding protein C ( MYBPC3 ) c.927-2A>G founder mutation accounts for >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. Methods We studied 60 probands with HCM caused by MYBPC3 c.927-2A>G and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped. Results Genetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+/LVH+), 59 G+without LVH (G+/LVH−) 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 but 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− 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. Conclusions Phenotypic expression of the Icelandic MYBPC3 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− individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation. Article in Journal/Newspaper Iceland The BMJ Open Heart 7 1 e001220 |
institution |
Open Polar |
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The BMJ |
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crjcrbmj |
language |
English |
description |
Objective The myosin-binding protein C ( MYBPC3 ) c.927-2A>G founder mutation accounts for >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. Methods We studied 60 probands with HCM caused by MYBPC3 c.927-2A>G and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped. Results Genetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+/LVH+), 59 G+without LVH (G+/LVH−) 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 but 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− 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. Conclusions Phenotypic expression of the Icelandic MYBPC3 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− individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation. |
author2 |
Akureyri Hospital Research Fund The Icelandic Cardiac Society Research Fund Landspitali–The National University Hospital of Iceland Research Fund Howard Hughes Medical Institute Foundation for the National Institutes of Health |
format |
Article in Journal/Newspaper |
author |
Adalsteinsdottir, Berglind Burke, Michael Maron, Barry J Danielsen, Ragnar Lopez, Begoña Diez, Javier Jarolim, Petr Seidman, Jonathan Seidman, Christine E. Ho, Carolyn Y Gunnarsson, Gunnar Th |
spellingShingle |
Adalsteinsdottir, Berglind Burke, Michael Maron, Barry J Danielsen, Ragnar Lopez, Begoña Diez, Javier Jarolim, Petr Seidman, Jonathan Seidman, Christine E. Ho, Carolyn Y Gunnarsson, Gunnar Th Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers |
author_facet |
Adalsteinsdottir, Berglind Burke, Michael Maron, Barry J Danielsen, Ragnar Lopez, Begoña Diez, Javier Jarolim, Petr Seidman, Jonathan Seidman, Christine E. Ho, Carolyn Y Gunnarsson, Gunnar Th |
author_sort |
Adalsteinsdottir, Berglind |
title |
Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers |
title_short |
Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers |
title_full |
Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers |
title_fullStr |
Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers |
title_full_unstemmed |
Hypertrophic cardiomyopathy in myosin-binding protein C ( MYBPC3) Icelandic founder mutation carriers |
title_sort |
hypertrophic cardiomyopathy in myosin-binding protein c ( mybpc3) icelandic founder mutation carriers |
publisher |
BMJ |
publishDate |
2020 |
url |
http://dx.doi.org/10.1136/openhrt-2019-001220 https://syndication.highwire.org/content/doi/10.1136/openhrt-2019-001220 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Open Heart volume 7, issue 1, page e001220 ISSN 2053-3624 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.1136/openhrt-2019-001220 |
container_title |
Open Heart |
container_volume |
7 |
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1 |
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e001220 |
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1811640374190407680 |