ArticleCirculation2011
Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes.
Article in Circulation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 293 citations in OpenAlex.
- International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework.Circulation. Genomic and precision medicine · 2021Trial
- Genotype-phenotype correlations in patients with pathogenic/likely pathogenic titin variants from the Swiss Arrhythmogenic Cardiomyopathy Registry.Open heart · 2026Observational
- Redox Imbalance and Genetic Mutations in Heart Failure: Synergistic Mechanisms and Therapeutic Strategies.Genes · 2026Review
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Functional Validation of a Novel HomozygousHuman mutation · 2026Article
- Titin Cardiomyopathy, Emerging Evidence: More Than A Big Heart.Current cardiology reports · 2025Review
- Left Ventricular Noncompaction Cardiomyopathy in Children: A Focus on Genetic and Molecular Mechanisms.Reviews in cardiovascular medicine · 2025Review
- Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases.International journal of molecular sciences · 2025Review
- The genetic landscape of pediatric postural orthostatic tachycardia syndrome.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025Article
- An overview of insights and updates on TTN mutations in cardiomyopathies.Frontiers in pharmacology · 2025Review
- Dilated Cardiomyopathy: A Genetic Journey from Past to Future.International journal of molecular sciences · 2024Review
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Arrhythmogenic right ventricular cardiomyopathy masquerading as peripartum cardiomyopathy.HeartRhythm case reports · 2024Article
- Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.Scientific reports · 2024Review
- A case report of isolated arrhythmogenic left ventricular cardiomyopathy: phenotypes, diagnosis, and treatment.European heart journal. Case reports · 2024Article
- Arrhythmogenic Right Ventricular Cardiomyopathy in Children: A Systematic Review.Diagnostics (Basel, Switzerland) · 2024Review
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Clinical and Genetic Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy Patients: A Single-Center Experience.Cardiology research · 2023Article
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Role of non-coding variants in cardiovascular disease.Journal of cellular and molecular medicine · 2023Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease characterized by fibrofatty replacement of the myocardium and a predisposition to cardiac arrhythmias and sudden death. We evaluated the cardiomyopathy gene titin (TTN) as a candidate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the titin protein to the transitional junction at intercalated disks. METHODS AND
resultsAll 312 titin exons known to be expressed in human cardiac titin and the complete 3' untranslated region were sequenced in 38 ARVC families. Eight unique TTN variants were detected in 7 families, including a prominent Thr2896Ile mutation that showed complete segregation with the ARVC phenotype in 1 large family. The Thr2896IIe mutation maps within a highly conserved immunoglobulin-like fold (Ig10 domain) located in the spring region of titin. Native gel electrophoresis, nuclear magnetic resonance, intrinsic fluorescence, and proteolysis assays of wild-type and mutant Ig10 domains revealed that the Thr2896IIe exchange reduces the structural stability and increases the propensity for degradation of the Ig10 domain. The phenotype of TTN variant carriers was characterized by a history of sudden death (5 of 7 families), progressive myocardial dysfunction causing death or heart transplantation (8 of 14 cases), frequent conduction disease (11 of 14), and incomplete penetrance (86%).
conclusionsOur data provide evidence that titin mutations can cause ARVC, a finding that further expands the origin of the disease beyond desmosomal proteins. Structural impairment of the titin spring is a likely cause of ARVC and constitutes a novel mechanism underlying myocardial remodeling and sudden cardiac death.
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