title: KCNH2 gene mutation: a potential link between epilepsy and long QT-2 syndrome.
abstract: Long QT syndrome (LQTS) is closely associated with syncope, seizure, and sudden death but LQTS is frequently misdiagnosed as epilepsy. LQTS and epilepsy both belong to the group of ion channelopathies that manifest in the heart and brain. Therefore, genetic analysis of genes associated with potassium and sodium homeostasis and electrical disorders may reveal a link between epilepsy and lethal cardiac arrhythmia. Here, the authors report a young woman who suffered recurrent seizure episodes and syncopes that occurred while walking and also during rest. She showed electroencephalogram abnormalities and a pathological prolonged QTc interval in electrocardiogram. The patient and the patient's asymptomatic family members underwent genetic screening of the three genes most frequently associated with LQTS: KCNQ1, KCNH2, and SCN5A. The patient and the family members did not show DNA alterations in the genes KCNQ1 and SCN5A associated with LQT-1 and LQT-3, respectively. However, the patient showed a de novo mutation 2587T→C in exon 10 of KCNH2 gene associated with LQT-2. The mutation caused a stop codon substitution (R863X) in the HERG channel, leading to a 296-amino acid deletion. The patient's asymptomatic relatives did not show the KCNH2 gene mutation. R863X alteration in HERG channel may be involved in both prolonged QTc interval and epilepsy. This fact raises the possibility that R863X alteration in KCNH2-encoded potassium channel may confer susceptibility for epilepsy and cardiac LQT-2 arrhythmia.
authors.affiliation: Cardiovascular Research Unit of the Cardiology Department, Cardiovascular Institute, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José J
authors.initials: JJ
authors.lastname: Zamorano-León
authors.forename: Rosa
authors.initials: R
authors.lastname: Yañez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Jaime
authors.forename: Pablo
authors.initials: P
authors.lastname: Rodriguez-Sierra
authors.forename: Laura
authors.initials: L
authors.lastname: Calatrava-Ledrado
authors.forename: Roman R
authors.initials: RR
authors.lastname: Alvarez-Granada
authors.forename: Petra Jiménez
authors.initials: PJ
authors.lastname: Mateos-Cáceres
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: López-Farré
mesh_terms: D001120:Arginine / Q000235:genetics; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: C496897:KCNN2 protein, human; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001120:Arginine