Mutations in the Cardiac Ryanodine Receptor Gene (hRyR2) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia

By S. Priori, C. Napolitano, N. Tiso, M. Memmi, G. Vignati, R. Bloise, V. Sorrentino, G. Danieli. Circulation, 2001

1,420 citations recorded by the source corpus.

BackgroundCatecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene (hRyR2) a likely candidate for this genetically transmitted arrhythmic disorder. Methods and ResultsTwelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction–amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. ConclusionsWe demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6f47402e549670d60c97db14e533e728d3cd3508

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

In Molecular Biology

Douglas P. Zipes

Citations in the corpus

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (2006, background): “Half of the autosomal dominant cases are caused by mutations in the gene encoding the cardiac ryanodine receptor (RyR2), responsible for calcium release from the stores of the sarcoplasmic reticulum.(831,832) The recessive form is caused by mutations in the gene encoding calsequestrin (CASQ2), a cal”
HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). (2011, background): “Summary of the Common CPVT Genes (Table 2) Two CPVT genetic variants have been identified: an autosomal dominant form, due to mutations in the gene encoding for the cardiac ryanodine receptor (RyR2), and a less common autosomal recessive form, resulting from mutations in the gene for cardiac calsequ”
HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). (2011, background): “Summary of the Common CPVT Genes (Table 2) Two CPVT genetic variants have been identified: an autosomal dominant form, due to mutations in the gene encoding for the cardiac ryanodine receptor (RyR2), and a less common autosomal recessive form, resulting from mutations in the gene for cardiac calsequ”