title: A novel variant in RyR2 causes familiar catecholaminergic polymorphic ventricular tachycardia.
abstract: Catecholaminergic polymorphic ventricular tachycardia is a rare familial arrhythmogenic disease. It usually occurs in juvenile patients with a structurally normal heart and causes exercise-emotion triggered syncope and sudden cardiac death. The main gene associated with catecholaminergic polymorphic ventricular tachycardia is RyR2, encoding the cardiac ryanodine receptor protein which is involved in calcium homeostasis. After the identification of a 16 year-old man presenting with exercise-induced sudden cardiac death, clinically diagnosed as catecholaminergic polymorphic ventricular tachycardia, we collected the family information and performed a comprehensive genetic analysis using Next Generation Sequencing technology. The initial electrocardiogram in the emergency department revealed ventricular fibrillation. On electrocardiogram monitoring, sinus tachycardia degenerated into bidirectional ventricular and into ventricular fibrillation. Catecholaminergic polymorphic ventricular tachycardia was clinically diagnosed in 5 of the 14 family members evaluated. There were no additional reports of seizures, pregnancy loss, neonatal death, or sudden cardiac death in family members. Genetic analysis of the index case identified only one rare novel variant p.Ile11Ser (c.32T>G) in the RyR2 gene. Subsequent familial analysis identified segregation of the genetic variant with the disease. All current evidence supports that novel p.Ile11Ser variant in the RyR2 gene is a potential disease-causing variant in catecholaminergic polymorphic ventricular tachycardia. To our knowledge, there has been no previous case report of catecholaminergic polymorphic ventricular tachycardia associated to this missense variant.
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosch
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Georgia
authors.initials: G
authors.lastname: Sarquella-Brugada
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Cesar
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Perez-Serra
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Coll
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Mademont
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Mates
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Del Olmo
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Private Praxis Pediatric Cardiology, Hamburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Petersen
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; Cardiovascular Genetics Unit, Hospital Josep Trueta, Girona, Spain. Electronic address: ramon@brugada.org.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004562:Electrocardiography; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000235:genetics*; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: C000621072:RyR2 protein, human; D019837:Ryanodine Receptor Calcium Release Channel
keywords: Catecholaminergic polymorphic ventricular tachycardia; Genetics; RyR2; Sudden cardiac death