title: Ryanodine receptor mutations presenting as idiopathic ventricular fibrillation: a report on two novel familial compound mutations, c.6224T>C and c.13781A>G, with the clinical presentation of idiopathic ventricular fibrillation.
abstract: Idiopathic ventricular fibrillation (IVF) is a rare genetically determined disease causing unexpected cardiac death in otherwise healthy individuals. This study identified two novel, functional heterozygous mutations in the ryanodine receptor 2 (RyR2) gene in a family with IVF. In the presented case all the patients received a thorough diagnostic workup to exclude structural heart disease. Blood was drawn from the patients, and genetic testing was performed including amplification and sequencing of splice locations in two exons of the RyR2 gene. The mutations were detected in five symptomatic family members. The genetic status of the five affected family members remains unclear. No clinically affected patient is without mutation. At this writing, one family member with confirmed mutation is asymptomatic. The differentiation between catecholaminergic polymorphic ventricular tachycardia (CPVT) and IVF remains a difficult issue, mainly based on clinical characteristics and gross genetic classification. In our case, the family history, exercise testing, and epinephrine stress testing do not suggest an association of arrhythmia and adrenergic triggers, which makes CPVT rather unlikely despite the fact that genetic testing showed RyR2 mutations. Currently, knowledge concerning the functional meaning of genetic mutations is growing. Future exploration of these functional aspects might give further impetus to allocation of these patients to a specific diagnosis.
authors.affiliation: Department for Pediatric Cardiology, University of Leipzig-Heart Center, Strümpellstrasse 39, 04289, Leipzig, Germany, christian.paech@med.uni-leipzig.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Paech
authors.forename: Roman Antonin
authors.initials: RA
authors.lastname: Gebauer
authors.forename: Jens
authors.initials: J
authors.lastname: Karstedt
authors.forename: Christoph
authors.initials: C
authors.lastname: Marschall
authors.forename: Andreas
authors.initials: A
authors.lastname: Bollmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Husser
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004562:Electrocardiography; D004837:Epinephrine; D005080:Exercise Test / Q000379:methods; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D014463:Ultrasonography; D014693:Ventricular Fibrillation / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D055815:Young Adult; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D004837:Epinephrine