Cardiac channel molecular autopsy for sudden unexpected death in epilepsy.
Sudden unexpected death in epilepsy is the sudden, unexplained, unexpected death of an individual with epilepsy in which postmortem examination does not reveal an anatomic or toxicologic cause of death. Patients with congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia have been frequently initially diagnosed with epilepsy. A cardiac channel molecular autopsy of the common long QT syndrome and catecholaminergic polymorphic ventricular tachycardia-susceptibility genes was performed on an archived necropsy specimen from an 8-year-old victim of sudden unexpected death in epilepsy. A novel, sporadic missense mutation in exon 104 of the RYR2-encoded ryanodine receptor/calcium release channel (c. 14806G>A, p.Gly4936Arg) was discovered. This mutation was absent in >600 reference alleles including both parents, involved a highly conserved amino acid, and localized to a key structure-function domain. To our knowledge, this is the first postmortem molecular diagnosis of catecholaminergic polymorphic ventricular tachycardia in a patient with sudden unexpected death in epilepsy.
Johnson
Jonathan N
JN
Department of Pediatrics/Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Tester
David J
DJ
Bass
Nancy E
NE
Ackerman
Michael J
MJ
D000483:Alleles; D001921:Brain / Q000503:physiopathology; D002648:Child; D016757:Death, Sudden, Cardiac; D004562:Electrocardiography; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D017180:Tachycardia, Ventricular / Q000150:complications / Q000235:genetics / Q000503:physiopathology
D019837:Ryanodine Receptor Calcium Release Channel