ArticleEBioMedicine2020
Identification, clinical manifestation and structural mechanisms of mutations in AMPK associated cardiac glycogen storage disease.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- AMPKγ2 Regulates Cardiac Hypertrophy and Arrhythmias via Interacting With Myosin.Circulation research · 2026Article
- Cardiomyopathy in glycogen storage diseases: diagnosis, prognosis, and advanced management.Heart failure reviews · 2026Review
- PRKAG2 Cardiomyopathy: A Case-Control Study on the Diagnostic Yield Of Histopathology and Ultrastructural Analysis from Endomyocardial Biopsy.Arquivos brasileiros de cardiologia · 2026Observational
- Cardiovascular involvement in glycogen storage diseases.Nature reviews. Cardiology · 2026Review
- Review
- Article
- When Paying Attention Pays Back: Missense Mutation c.1006G>A p. (Val336Ile) inInternational journal of molecular sciences · 2024Review
- Post-mortem genetic analysis of sudden unexplained death in a young cohort: a whole-exome sequencing study.International journal of legal medicine · 2023Article
- Advances in basic and translational research in atrial fibrillation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Intrafamilial Phenotypical Variability Linked to PRKAG2 Mutation-Family Case Report and Review of the Literature.Life (Basel, Switzerland) · 2022Review
- Right Ventricle Involvement by Glycogen Storage Cardiomyopathy (PRKAG2): Standard and Advanced Echocardiography Analyses.Arquivos brasileiros de cardiologia · 2022Article
- Genetic variants in Colombian patients with inherited cardiac conditions.Molecular genetics & genomic medicine · 2022Article
- Atrial Flutter in PRKAG2 Syndrome: Clinical and Electrophysiological Characteristics.Arquivos brasileiros de cardiologia · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Journal of arrhythmia · 2022Article
- Controversial molecular functions of CBS versus non-CBS domain variants of PRKAG2 in arrhythmia and cardiomyopathy: A case report and literature review.Molecular genetics & genomic medicine · 2022Review
- AKT-mTOR signaling-mediated rescue ofCardiovascular diagnosis and therapy · 2022Article
- Case Report: Family Curse: AnFrontiers in cardiovascular medicine · 2022Article
- Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort.Scientific reports · 2020Article
- Too much sugar leaves a sour taste: A cardiac disease caused by excess glycogen deposit.EBioMedicine · 2020Article
Corrections and comments
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- Erratum issued
Authors and funding
20 authors at 9 institutions in 6 countries.
Funding
Abstract
backgroundAlthough 21 causative mutations have been associated with PRKAG2 syndrome, our understanding of the syndrome remains incomplete. The aim of this project is to further investigate its unique genetic background, clinical manifestations, and underlying structural changes.
methodsWe recruited 885 hypertrophic cardiomyopathy (HCM) probands and their families internationally. Targeted next-generation sequencing of sudden cardiac death (SCD) genes was performed. The role of the identified variants was assessed using histological techniques and computational modeling.
findingsTwelve PRKAG2 syndrome kindreds harboring 5 distinct variants were identified. The clinical penetrance of 25 carriers was 100.0%. Twenty-two family members died of SCD or heart failure (HF). All probands developed bradycardia (HRmin, 36.3 ± 9.8 bpm) and cardiac conduction defects, and 33% had evidence of atrial fibrillation/paroxysmal supraventricular tachycardia (PSVT) and 67% had ventricular preexcitation, respectively. Some carriers presented with apical hypertrophy, hypertension, hyperlipidemia, and renal insufficiency. Histological study revealed reduced AMPK activity and major cardiac channels in the heart tissue with K485E mutation. Computational modelling suggests that K485E disrupts the salt bridge connecting the β and γ subunits of AMPK, R302Q/P decreases the binding affinity for ATP, T400N and H401D alter the orientation of H383 and R531 residues, thus altering nucleotide binding, and N488I and L341S lead to structural instability in the Bateman domain, which disrupts the intramolecular regulation.
interpretationIncluding 4 families with 3 new mutations, we describe a cohort of 12 kindreds with PRKAG2 syndrome with novel pathogenic mechanisms by computational modelling. Severe clinical cardiac phenotypes may be developed, including HF, requiring close follow-up.
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