PRKAG2 cardiac syndrome: familial ventricular preexcitation, conduction system disease, and cardiac hypertrophy.
Genetic studies of families with inherited cardiac rhythm disturbances have established a molecular basis for ventricular arrhythmogenic disorders. Genes responsible for the long QT syndrome, Brugada syndrome, and polymorphic ventricular tachycardia have been identified. The elucidation of genetic defects responsible for more commonly occurring supraventricular rhythm disturbances have not been as forthcoming, with the exception of SCN5A mutations known to cause conduction system disease. Recently, we identified the genetic cause of a familial arrhythmogenic syndrome characterized by ventricular preexcitation and tachyarrhythmias (Wolff-Parkinson-White syndrome), progressive conduction system disease, and cardiac hypertrophy. The causative gene was shown to be the gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase. The role of AMP-activated protein kinase in the regulation of the glucose metabolic pathway in muscle suggests that genetic defects in PRKAG2 may induce a previously undescribed cardiac glycogenosis syndrome.
Gollob
Michael H
MH
Division of Cardiology, University of Western Ontario, London Health Sciences Center, Ontario, Canada. mgollob@uwo.ca
Green
Martin S
MS
Tang
Anthony S L
AS
Roberts
Robert
R
D055372:AMP-Activated Protein Kinases; D000328:Adult; D006332:Cardiomegaly / Q000150:complications / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics*; D011226:Pre-Excitation Syndromes / Q000150:complications / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases