ArticleEuropean heart journal2018
A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta.
Article in European heart journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 6 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 6 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.BMC genomics · 2024Pooled it
- Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease.Physiological genomics · 2023Pooled it
- Oligogenic Architecture of Rare Noncoding Variants Distinguishes 4 Congenital Heart Disease Phenotypes.Circulation. Genomic and precision medicine · 2023Pooled it
- Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias.JAMA network open · 2022Pooled it
- Isolated Coarctation of the Aorta: Current Concepts and Perspectives.Frontiers in cardiovascular medicine · 2022Pooled it
- Prevalence of Intracranial Aneurysm in Patients with Aortopathy: A Systematic Review with Meta-Analyses.Journal of stroke · 2020Pooled it
- Diagnostic Yield of Exome Sequencing in Patients With Congenital Heart Disease From Southern Africa.Circulation. Genomic and precision medicine · 2026Article
- Selenotrisulfide delivery restores redox balance in myocardial infarction via a thiol-exchange reactionBioactive materials · 2026Article
- MYH6 in Congenital Heart Defects: A Genotype-Phenotype Characterization in a French Cohort.Pediatric cardiology · 2026Article
- The Role of Next-Generation Sequencing in the Management of Asymptomatic, Young Slovenian Athletes for Distinction Between Athlete's Heart and Cardiomyopathy.Biomedicines · 2026Article
- Article
- Origins of Aortic Coarctation: A Vascular Smooth Muscle Compartment Boundary Model.Journal of developmental biology · 2025Article
- Age Differences in Aortic Stenosis.Reviews in cardiovascular medicine · 2025Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications.American journal of human genetics · 2024Article
- Tetralogy of Fallot: variants of MYH6 gene promoter and cellular functional analyses.Pediatric research · 2024Article
- 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2024Review
- Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.medRxiv : the preprint server for health sciences · 2024Article
- Human Genetics of Congenital Heart Defects.Advances in experimental medicine and biology · 2024Review
- Case-control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India.BMC pediatrics · 2023Article
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aims: Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA. Methods and results: We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10-22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation. Conclusion: Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.
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