Gene panel testing in epileptic encephalopathies and familial epilepsies

Rikke S. Møller, Line H G Larsen, Katrine M. Johannesen, Inga Talvik, Tiina Talvik, Ulvi Vaher, Maria J. Miranda, Muhammad Farooq, Jens E K Nielsen, Lene Lavard Svendsen, Ditte B. Kjelgaard, Karen M. Linnet, Qin Hao, Peter Uldall, Mimoza Frangu, Niels Tommerup, Shahid M. Baig, Uzma Abdullah, Alfred P. Born, Pia GellertMarina Nikanorova, Kern Olofsson, Birgit Jepsen, Dragan Marjanovic, Lana I K Al-Zehhawi, Sofia J. Peñalva, Bente Krag-Olsen, Klaus Brusgaard, Helle Hjalgrim, Guido Rubboli, Deb K. Pal, Hans A. Dahl

Research output: Contribution to journalArticle

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 including SCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2, and STX1B. 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.

Original languageEnglish
Pages (from-to)210-219
Number of pages10
JournalMolecular Syndromology
Volume7
Issue number4
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • Epileptic encephalopathies
  • Familial epilepsies
  • Gene panel testing
  • Seizures

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Møller, R. S., Larsen, L. H. G., Johannesen, K. M., Talvik, I., Talvik, T., Vaher, U., Miranda, M. J., Farooq, M., Nielsen, J. E. K., Lavard Svendsen, L., Kjelgaard, D. B., Linnet, K. M., Hao, Q., Uldall, P., Frangu, M., Tommerup, N., Baig, S. M., Abdullah, U., Born, A. P., ... Dahl, H. A. (2016). Gene panel testing in epileptic encephalopathies and familial epilepsies. Molecular Syndromology, 7(4), 210-219. https://doi.org/10.1159/000448369