Katia Hardies1, Sarah Weckhuysen, Elke Peeters, Philip Holmgren, Hilde Van Esch, Peter De Jonghe, Wim Van Paesschen, Arvid Suls. 1. From the Neurogenetics Group (K.H., S.W., P.H., P.D.J., A.S.), Department of Molecular Genetics, VIB, Antwerp; Laboratory of Neurogenetics (K.H., S.W., P.H., P.D.J., A.S.), Institute Born-Bunge, University of Antwerp; Department of Neurology (E.P., W.V.P.), University Hospital Gasthuisberg, Leuven; Center for Human Genetics (H.V.E.), University Hospitals Leuven, KU Leuven; and Division of Neurology (P.D.J.), Antwerp University Hospital, Antwerp, Belgium.
Abstract
OBJECTIVES: After we identified a 17q12 duplication cosegregating in a 4-generation family with genetic or generalized epilepsy with febrile seizures plus (GEFS+), we aimed to determine the frequency of 17q12 genomic rearrangements in GEFS+ and a wide spectrum of other epilepsy phenotypes. We furthermore describe seizure prevalence in previously reported patients with a 17q12 duplication or deletion. METHODS: We analyzed 433 patients with a broad range of epilepsy phenotypes. The 180k Cytosure ISCA v2 array was used for copy number variation screening in the index patient. Segregation analysis and follow-up studies were performed with the multiplex amplicon quantification technique. RESULTS: We identified 2 families in which a 17q12 duplication segregated with febrile-sensitive epilepsy. In the follow-up study, the mutation rate in familial febrile seizures (FS) and GEFS+ phenotypes was 1/222. No 17q12 deletions were detected. Two of the 6 mutation carriers in the initial GEFS+ family had mild intellectual disability, whereas all family members of the second family were of normal intelligence. In the literature, 4 of 43 individuals with a 17q12 duplication and 4 of 55 with the reciprocal deletion were described to have had seizures. CONCLUSIONS: Our study shows that 17q12 duplications are a rare cause of familial FS and GEFS+. Although some family members might have intellectual disability, seizures can be the sole clinical symptom. This is the first report on an inherited copy number variation in these self-limiting fever-sensitive epilepsy syndromes, potentially revealing a novel pathomechanism involved in familial FS and GEFS+.
OBJECTIVES: After we identified a 17q12 duplication cosegregating in a 4-generation family with genetic or generalized epilepsy with febrile seizures plus (GEFS+), we aimed to determine the frequency of 17q12 genomic rearrangements in GEFS+ and a wide spectrum of other epilepsy phenotypes. We furthermore describe seizure prevalence in previously reported patients with a 17q12 duplication or deletion. METHODS: We analyzed 433 patients with a broad range of epilepsy phenotypes. The 180k Cytosure ISCA v2 array was used for copy number variation screening in the index patient. Segregation analysis and follow-up studies were performed with the multiplex amplicon quantification technique. RESULTS: We identified 2 families in which a 17q12 duplication segregated with febrile-sensitive epilepsy. In the follow-up study, the mutation rate in familial febrile seizures (FS) and GEFS+ phenotypes was 1/222. No 17q12 deletions were detected. Two of the 6 mutation carriers in the initial GEFS+ family had mild intellectual disability, whereas all family members of the second family were of normal intelligence. In the literature, 4 of 43 individuals with a 17q12 duplication and 4 of 55 with the reciprocal deletion were described to have had seizures. CONCLUSIONS: Our study shows that 17q12 duplications are a rare cause of familial FS and GEFS+. Although some family members might have intellectual disability, seizures can be the sole clinical symptom. This is the first report on an inherited copy number variation in these self-limiting fever-sensitive epilepsy syndromes, potentially revealing a novel pathomechanism involved in familial FS and GEFS+.
Authors: Corinna Hartmann; Sarah von Spiczak; Arvid Suls; Sarah Weckhuysen; Gunnar Buyse; Catheline Vilain; Patrick Van Bogaert; Peter De Jonghe; Joseph Cook; Hiltrud Muhle; Ulrich Stephani; Ingo Helbig; Heather C Mefford Journal: Epilepsia Date: 2015-02-17 Impact factor: 5.864
Authors: Jennifer A Kearney; Letonia D Copeland-Hardin; Samantha Duarte; Nicole A Zachwieja; Isaiah K Eckart-Frank; Nicole A Hawkins Journal: Mamm Genome Date: 2022-05-23 Impact factor: 3.224
Authors: Jenny E Wight; Viet-Huong Nguyen; Marco T Medina; Christopher Patterson; Reyna M Durón; Yolly Molina; Yu-Chen Lin; Iris E Martínez-Juárez; Adriana Ochoa; Aurelio Jara-Prado; Miyabi Tanaka; Dongsheng Bai; Sumaya Aftab; Julia N Bailey; Antonio V Delgado-Escueta Journal: Mol Genet Genomic Med Date: 2016-01-23 Impact factor: 2.183