title: A missense mutation in CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel.
abstract: Catecholamine-induced polymorphic ventricular tachycardia (CPVT) 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. We have recently described an autosomal recessive form of the disorder in seven families from a Bedouin tribe in the north of Israel, and mapped the disease-causing gene to chromosome 1p13-1p21. Direct sequencing of the 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 pathophysiologic events underlying ventricular tachycardia, and to the use of drugs directly involved in intracellular calcium control for the treatment of the CPVT patients.
authors.affiliation: Heart Institute, Sheba Medical Center, Tel Hashomer, Israel. hadas11@barak.net.il
authors.forename: Hadas
authors.initials: H
authors.lastname: Lahat
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.forename: Michael
authors.initials: M
authors.lastname: Eldar
mesh_terms: D000293:Adolescent; D018912:Arabs / Q000235:genetics; D002155:Calsequestrin / Q000737:chemistry / Q000235:genetics*; D002395:Catecholamines / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005192:Family Health; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007557:Israel; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D011487:Protein Conformation; D013575:Syncope / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000235:genetics / Q000503:physiopathology*
chemical_list: C443109:CASQ2 protein, human; D002155:Calsequestrin; D002395:Catecholamines