Felix von Podewils1, Victoria Kowoll2, Winnie Schroeder3, Julia Geithner4, Zhong I Wang5, Bernadette Gaida2, Paula Bombach2, Christof Kessler2, Ute Felbor3, Uwe Runge2. 1. Department of Neurology, Epilepsy Center, University of Greifswald, Greifswald, Germany. Electronic address: felix.schneider@uni-greifswald.de. 2. Department of Neurology, Epilepsy Center, University of Greifswald, Greifswald, Germany. 3. Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, Ernst Moritz Arndt University, Greifswald, Germany. 4. Department of Neurology, Epilepsy Center, University of Greifswald, Greifswald, Germany; Epilepsy Center Berlin-Brandenburg, Berlin, Germany. 5. Epilepsy Center, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Abstract
OBJECTIVE: This study aimed to determine the contribution of EFHC1 variants to the phenotypic variability of juvenile myoclonic epilepsy (JME) and to evaluate their diagnostic value regarding previously identified clinical long-term seizure outcome predictors in a consecutive cohort of patients with JME. METHODS: Thirty-eight probands and three family members affected with JME were studied at a tertiary epilepsy center with a review of their medical records and a subsequent face-to-face interview. All coding EFHC1 exons and adjacent exon/intron boundaries were directly sequenced. RESULTS: The previously reported EFHC1 mutation F229L was found in two cases who presented with early generalized tonic-clonic seizure (GTCS) onset and appeared to be associated with milder subtypes of JME. Variant R294H was identified in two further probands who had a subtype of JME developing from childhood absence epilepsy. However, segregation of the phenotype with this variant could not be confirmed in one family. CONCLUSIONS: Our findings corroborate the heterogeneity of JME as an electroclinical epilepsy syndrome and provide evidence that genetic factors may influence and help predict the long-term seizure outcome in patients with JME.
OBJECTIVE: This study aimed to determine the contribution of EFHC1 variants to the phenotypic variability of juvenile myoclonic epilepsy (JME) and to evaluate their diagnostic value regarding previously identified clinical long-term seizure outcome predictors in a consecutive cohort of patients with JME. METHODS: Thirty-eight probands and three family members affected with JME were studied at a tertiary epilepsy center with a review of their medical records and a subsequent face-to-face interview. All coding EFHC1 exons and adjacent exon/intron boundaries were directly sequenced. RESULTS: The previously reported EFHC1 mutation F229L was found in two cases who presented with early generalized tonic-clonic seizure (GTCS) onset and appeared to be associated with milder subtypes of JME. Variant R294H was identified in two further probands who had a subtype of JME developing from childhood absence epilepsy. However, segregation of the phenotype with this variant could not be confirmed in one family. CONCLUSIONS: Our findings corroborate the heterogeneity of JME as an electroclinical epilepsy syndrome and provide evidence that genetic factors may influence and help predict the long-term seizure outcome in patients with JME.
Authors: Julia N Bailey; Christopher Patterson; Laurence de Nijs; Reyna M Durón; Viet-Huong Nguyen; Miyabi Tanaka; Marco T Medina; Aurelio Jara-Prado; Iris E Martínez-Juárez; Adriana Ochoa; Yolli Molina; Toshimitsu Suzuki; María E Alonso; Jenny E Wight; Yu-Chen Lin; Laura Guilhoto; Elza Marcia Targas Yacubian; Jesús Machado-Salas; Andrea Daga; Kazuhiro Yamakawa; Thierry M Grisar; Bernard Lakaye; Antonio V Delgado-Escueta Journal: Genet Med Date: 2016-07-28 Impact factor: 8.822