Hypertrophic cardiomyopathy in myosin-binding protein C (MYBPC3) Icelandic founder mutation carriers
ObjectiveThe 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 mutat...
Published in: | Open Heart |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMJ Publishing Group
2020
|
Subjects: | |
Online Access: | https://doi.org/10.1136/openhrt-2019-001220 https://doaj.org/article/0a0ffdf5fecb4f7f9c6f2cb2df7a069d |
id |
ftdoajarticles:oai:doaj.org/article:0a0ffdf5fecb4f7f9c6f2cb2df7a069d |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:0a0ffdf5fecb4f7f9c6f2cb2df7a069d 2023-05-15T16:51:48+02:00 Hypertrophic cardiomyopathy in myosin-binding protein C (MYBPC3) Icelandic founder mutation carriers Javier Diez Begoña López Barry J Maron Berglind Adalsteinsdottir Michael Burke Ragnar Danielsen Petr Jarolim Jonathan Seidman Christine E. Seidman Carolyn Y Ho Gunnar Th Gunnarsson 2020-06-01T00:00:00Z https://doi.org/10.1136/openhrt-2019-001220 https://doaj.org/article/0a0ffdf5fecb4f7f9c6f2cb2df7a069d EN eng BMJ Publishing Group https://openheart.bmj.com/content/7/1/e001220.full https://doaj.org/toc/2053-3624 doi:10.1136/openhrt-2019-001220 2053-3624 https://doaj.org/article/0a0ffdf5fecb4f7f9c6f2cb2df7a069d Open Heart, Vol 7, Iss 1 (2020) Diseases of the circulatory (Cardiovascular) system RC666-701 article 2020 ftdoajarticles https://doi.org/10.1136/openhrt-2019-001220 2022-12-31T06:17:48Z ObjectiveThe 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.MethodsWe 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.ResultsGenetic 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.ConclusionsPhenotypic 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 Directory of Open Access Journals: DOAJ Articles Open Heart 7 1 e001220 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Diseases of the circulatory (Cardiovascular) system RC666-701 |
spellingShingle |
Diseases of the circulatory (Cardiovascular) system RC666-701 Javier Diez Begoña López Barry J Maron Berglind Adalsteinsdottir Michael Burke Ragnar Danielsen Petr Jarolim Jonathan Seidman Christine E. Seidman Carolyn Y Ho Gunnar Th Gunnarsson Hypertrophic cardiomyopathy in myosin-binding protein C (MYBPC3) Icelandic founder mutation carriers |
topic_facet |
Diseases of the circulatory (Cardiovascular) system RC666-701 |
description |
ObjectiveThe 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.MethodsWe 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.ResultsGenetic 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.ConclusionsPhenotypic 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. |
format |
Article in Journal/Newspaper |
author |
Javier Diez Begoña López Barry J Maron Berglind Adalsteinsdottir Michael Burke Ragnar Danielsen Petr Jarolim Jonathan Seidman Christine E. Seidman Carolyn Y Ho Gunnar Th Gunnarsson |
author_facet |
Javier Diez Begoña López Barry J Maron Berglind Adalsteinsdottir Michael Burke Ragnar Danielsen Petr Jarolim Jonathan Seidman Christine E. Seidman Carolyn Y Ho Gunnar Th Gunnarsson |
author_sort |
Javier Diez |
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 Publishing Group |
publishDate |
2020 |
url |
https://doi.org/10.1136/openhrt-2019-001220 https://doaj.org/article/0a0ffdf5fecb4f7f9c6f2cb2df7a069d |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Open Heart, Vol 7, Iss 1 (2020) |
op_relation |
https://openheart.bmj.com/content/7/1/e001220.full https://doaj.org/toc/2053-3624 doi:10.1136/openhrt-2019-001220 2053-3624 https://doaj.org/article/0a0ffdf5fecb4f7f9c6f2cb2df7a069d |
op_doi |
https://doi.org/10.1136/openhrt-2019-001220 |
container_title |
Open Heart |
container_volume |
7 |
container_issue |
1 |
container_start_page |
e001220 |
_version_ |
1766041886248665088 |