Identifying Sarcomere Gene Mutations in Hypertrophic Cardiomyopathy: A Personal History
Open accessAbstract
This review provides an historical and personal perspective on the discovery of genetic causes for hypertrophic cardiomyopathy (HCM). Extraordinary insights by physicians who initially detailed remarkable and varied manifestations of the disorder, collaboration among multidisciplinary teams with skills in clinical diagnostics and molecular genetics, and hard work by scores of trainees solved the etiologic riddle of HCM and unexpectedly demonstrated mutations in sarcomere protein genes as the cause of disease. In addition to celebrating 20 years of genetic research in HCM, this article serves as an introductory overview to a thematic review series that will present contemporary advances in the field of hypertrophic heart disease. Through the continued application of advances in genetic methodologies, combined with biochemical and biophysical analyses of the consequences of human mutations, fundamental knowledge about HCM and sarcomere biology has emerged. Expanding research to elucidate the mechanisms by which subtle genetic variation in contractile proteins remodel the human heart remains an exciting opportunity, one with considerable promise to provide new strategies to limit or even prevent HCM pathogenesis.
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The model identified 447 genes whose loss was predicted to shift cardiomyocytes towards the hypertrophic cardiomyopathy state, which were enriched for pathways including Titin binding and sarcomere organization known to impact hypertrophic cardiomyopathy pathogenesis.
“Overall, the model identified 447 genes whose loss was predicted to shift cardiomyocytes towards the hypertrophic cardiomyopathy state, which were enriched for pathways including Titin binding36 and sarcomere organization37 known to impact hypertrophic cardiomyopathy pathogenesis.”
From Transfer learning enables predictions in network biology (2023) · cites this paper as [37]
HCM is linked to mutations in genes encoding sarcomeric proteins.
“HCM is highly heterogeneous and has been linked to mutations in the genes that encode proteins of the sarcomere, with over 1,400 HCM-associated mutations identified in at least 11 sarcomeric proteins (1, 5).”
From Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics (2020) · cites this paper as [5]
Over 1,400 HCM-associated mutations have been identified in at least 11 sarcomeric proteins.
“HCM is highly heterogeneous and has been linked to mutations in the genes that encode proteins of the sarcomere, with over 1,400 HCM-associated mutations identified in at least 11 sarcomeric proteins (1, 5).”
From Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics (2020) · cites this paper as [5]
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Transfer learning enables predictions in network biology
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Advances in the Genetic Basis and Pathogenesis of Sarcomere Cardiomyopathies
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- Authors
- Seidman, C. E., & Seidman, J. G.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Circulation Research
- Published
- 2011-03-18
- Volume
- 108
- Issue
- 6
- Pages
- 743-750
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC3072749
- OpenAlex
- W2100906399
- Cited by
- 271
- References
- 97
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 15 · 2023: 20 · 2022: 10 · 2021: 28 · 2020: 15 · 2019: 13 · 2018: 12 · 2017: 21 · 2016: 24 · 2015: 12 · 2014: 34 · 2013: 17 · 2012: 21
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Fondation Leducq
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL084553, R01HL080494)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- hypertrophic cardiomyopathy, sarcomere gene mutations, sarcomere proteins, genetic etiology, contractile proteins, cardiac remodeling
- MeSH terms
- Cardiomyopathy, Hypertrophic, Humans, Mutation, Myocardium, Sarcomeres, Genetic Variation, Molecular Probe Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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