title: Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.
abstract: In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing. The patients had a range of different epilepsies from benign neonatal seizures to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease-causing variant in 49 (23%) of the 216 patients. The variants were found in 19 different genes includingSCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2,andSTX1B. Patients with neonatal-onset epilepsies had the highest rate of positive findings (57%). The overall yield for patients with EEs was 32%, compared to 17% among patients with generalized epilepsies and 16% in patients with focal or multifocal epilepsies. By the use of a gene panel consisting of 46 epilepsy genes, we were able to find a disease-causing genetic variation in 23% of the analyzed patients. The highest yield was found among patients with neonatal-onset epilepsies and EEs.
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark; Institute for Regional Health Services, University of Southern Denmark, Denmark.
authors: Rikke S
authors: RS
authors: Møller
authors: Amplexa Genetics, Odense, Denmark.
authors: Line H G
authors: LH
authors: Larsen
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark; Institute for Regional Health Services, University of Southern Denmark, Denmark.
authors: Katrine M
authors: KM
authors: Johannesen
authors: Tallinn Children's Hospital, Tallinn, Estonia; Tartu University Hospital, Children's Clinic, Tartu, Estonia.
authors: Inga
authors: I
authors: Talvik
authors: Tartu University Hospital, Children's Clinic, Tartu, Estonia; Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors: Tiina
authors: T
authors: Talvik
authors: Tartu University Hospital, Children's Clinic, Tartu, Estonia; Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors: Ulvi
authors: U
authors: Vaher
authors: Department of Pediatrics, Pediatric Neurology, Herlev University Hospital, Copenhagen University, Herlev, Denmark.
authors: Maria J
authors: MJ
authors: Miranda
authors: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark; Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS, Faisalabad, Pakistan.
authors: Muhammad
authors: M
authors: Farooq
authors: Department of Clinical Medicine, Section of Gynaecology, Obstetrics and Paediatrics, Roskilde Hospital, Roskilde, Denmark.
authors: Jens E K
authors: JE
authors: Nielsen
authors: Department of Pediatrics, Hvidovre Hospital, Hvidovre, Denmark.
authors: Lene Lavard
authors: LL
authors: Svendsen
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark.
authors: Ditte B
authors: DB
authors: Kjelgaard
authors: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors: Karen M
authors: KM
authors: Linnet
authors: Amplexa Genetics, Odense, Denmark.
authors: Qin
authors: Q
authors: Hao
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark.
authors: Peter
authors: P
authors: Uldall
authors: Department of Pediatrics, Holbæk Hospital, Holbæk, Denmark.
authors: Mimoza
authors: M
authors: Frangu
authors: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
authors: Niels
authors: N
authors: Tommerup
authors: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS, Faisalabad, Pakistan.
authors: Shahid M
authors: SM
authors: Baig
authors: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark; Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE)-PIEAS, Faisalabad, Pakistan.
authors: Uzma
authors: U
authors: Abdullah
authors: Department of Paediatrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors: Alfred P
authors: AP
authors: Born
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark.
authors: Pia
authors: P
authors: Gellert
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark; Institute for Regional Health Services, University of Southern Denmark, Denmark.
authors: Marina
authors: M
authors: Nikanorova
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark.
authors: Kern
authors: K
authors: Olofsson
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark.
authors: Birgit
authors: B
authors: Jepsen
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark.
authors: Dragan
authors: D
authors: Marjanovic
authors: Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
authors: Lana I K
authors: LI
authors: Al-Zehhawi
authors: CEMIC, Department of Genetics, Buenos Aires, Argentina.
authors: Sofia J
authors: SJ
authors: Peñalva
authors: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors: Bente
authors: B
authors: Krag-Olsen
authors: Amplexa Genetics, Odense, Denmark.
authors: Klaus
authors: K
authors: Brusgaard
authors: Danish Epilepsy Centre, University of Southern Denmark, Denmark; Institute for Regional Health Services, University of Southern Denmark, Denmark.
authors: Helle
authors: H
authors: Hjalgrim
authors: Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark.
authors: Guido
authors: G
authors: Rubboli
authors: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors: Deb K
authors: DK
authors: Pal
authors: Amplexa Genetics, Odense, Denmark.
authors: Hans A
authors: HA
authors: Dahl
keywords: Epileptic encephalopathies; Familial epilepsies; Gene panel testing; Seizures