ArticleJournal of medical genetics2013
Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing.
Article in Journal of medical genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 244 citations in OpenAlex.
- Functional Validation of a Novel HomozygousHuman mutation · 2026Article
- Integrative transcriptomic analysis revealed the roles and prognostic value of ion channels in hypertrophic cardiomyopathy.Frontiers in pharmacology · 2026Article
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- Genetic determinants of the phenotype in a Swedish cohort of patients with hypertrophic cardiomyopathy.Scientific reports · 2025Article
- Clinically Actionable Hypertrophic Cardiomyopathy Genes in South Asian Indian Patients.Journal of the American Heart Association · 2025Article
- The clinical and genetic spectrum of pediatric hypertrophic cardiomyopathy manifesting before one year of age.Pediatric research · 2025Article
- Left ventricular septal convexity in differentiating hypertrophic cardiomyopathy from hypertensive heart disease - a cardiac magnetic resonance study.Scientific reports · 2025Article
- Article
- A Case Study Identified a New Mutation in theInternational journal of general medicine · 2025Article
- Identification of candidate cardiomyopathy modifier genes through genome sequencing and RNA profiling.Frontiers in cardiovascular medicine · 2025Article
- Troponin I - a comprehensive review of its function, structure, evolution, and role in muscle diseases.Animal cells and systems · 2025Review
- Investigation of mutation spectrum amongst patients with familial primary cardiomyopathy using targeted NGS in Indian population.Journal of applied genetics · 2024Article
- Review
- Sudden Cardiac Death, Post-Mortem Investigation: A Proposing Panel of First Line and Second Line Genetic Tests.Journal of personalized medicine · 2024Review
- Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.Scientific reports · 2024Review
- MYH7 in cardiomyopathy and skeletal muscle myopathy.Molecular and cellular biochemistry · 2024Review
- Left ventricular hypertrophy. Is there only hypertrophic cardiomyopathy?Archivos de cardiologia de Mexico · 2024Article
- The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye.Anatolian journal of cardiology · 2023Article
- Structure determination and analysis of titin A-band fibronectin type III domains provides insights for disease-linked variants and protein oligomerisation.Journal of structural biology · 2023Article
- Hypertrophic Cardiomyopathy in a Latin American Center: A Single Center Observational Study.Journal of clinical medicine · 2023Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundClinical interpretation of the large number of rare variants identified by high throughput sequencing (HTS) technologies is challenging. The aim of this study was to explore the clinical implications of a HTS strategy for patients with hypertrophic cardiomyopathy (HCM) using a targeted HTS methodology and workflow developed for patients with a range of inherited cardiovascular diseases. By comparing the sequencing results with published findings and with sequence data from a large-scale exome sequencing screen of UK individuals, we sought to quantify the strength of the evidence supporting causality for detected candidate variants. METHODS AND
results223 unrelated patients with HCM (46±15 years at diagnosis, 74% males) were studied. In order to analyse coding, intronic and regulatory regions of 41 cardiovascular genes, we used solution-based sequence capture followed by massive parallel resequencing on Illumina GAIIx. Average read-depth in the 2.1 Mb target region was 120. Rare (frequency<0.5%) non-synonymous, loss-of-function and splice-site variants were defined as candidates. Excluding titin, we identified 152 distinct candidate variants in sarcomeric or associated genes (89 novel) in 143 patients (64%). Four sarcomeric genes (MYH7, MYBPC3, TNNI3, TNNT2) showed an excess of rare single non-synonymous single-nucleotide polymorphisms (nsSNPs) in cases compared to controls. The estimated probability that a nsSNP in these genes is pathogenic varied between 57% and near certainty depending on the location. We detected an additional 94 candidate variants (73 novel) in desmosomal, and ion-channel genes in 96 patients (43%).
conclusionsThis study provides the first large-scale quantitative analysis of the prevalence of sarcomere protein gene variants in patients with HCM using HTS technology. Inclusion of other genes implicated in inherited cardiac disease identifies a large number of non-synonymous rare variants of unknown clinical significance.
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