Autosomal recessive catecholamine-induced polymorphic ventricular tachycardia.
Catecholamine-induced polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures or sudden death, in response to physical activity or emotional stress, and affects mainly young children with morphologically normal hearts. An autosomal recessive form of the disorder in seven families from a Bedouin tribe in the north of Israel was recently described by the authors, and the disease-causing gene was mapped to chromosome 1p13-1p21. Direct sequencing of calsequestrin 2 (CASQ2), a candidate gene from within the linkage interval, revealed a negatively charged aspartic acid change to a positively charged histidine at position 307 of the protein. CASQ2 serves as the major calcium reservoir within cardiac myocytes. This mutation occurs in a highly conserved residue of the protein. The implication of the calcium release cascade in this disease may lead to a better understanding of the pathophysiological events underlying ventricular tachycardia, and to the use of drugs directly involved in intracellular calcium control for the treatment of the PVT patients.
Lahat
Hadas
H
Danek Gartner Institute of Human Genetics, Neufeld Cardiac Research Institute and Heart Institute, Sheba Medical Center Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pras
Elon
E
Eldar
Michael
M