University of Oulu

Jonna Komulainen-Ebrahim, John M. Schreiber, Salla M. Kangas, Katri Pylkäs, Maria Suo-Palosaari, Elisa Rahikkala, Johanna Liinamaa, Esa-Ville Immonen, Ilmo Hassinen, Päivi Myllynen, Heikki Rantala, Reetta Hinttala, Johanna Uusimaa, Novel variants and phenotypes widen the phenotypic spectrum of GABRG2-related disorders, Seizure, Volume 69, 2019, Pages 99-104, ISSN 1059-1311,

Novel variants and phenotypes widen the phenotypic spectrum of GABRG2-related disorders

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Author: Komulainen-Ebrahim, Jonna1,2,3,4; Schreiber, John M.5; Kangas, Salla M.1,2,3;
Organizations: 1PEDEGO Research Unit, University of Oulu, Oulu, Finland
2Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
3Biocenter Oulu, University of Oulu, Oulu, Finland
4Department of Children and Adolescents, Division of Pediatric Neurology, Oulu University Hospital, Oulu, Finland
5Epilepsy and Clinical Neurophysiology, Children’s National Health System, Washington, DC, USA
6Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
7Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
8Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
9Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland
10Department of Ophthalmology, Oulu University Hospital, Oulu, Finland
11Nano and Molecular Systems Research Unit, University of Oulu, Oulu, Finland
12Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
13Department of Clinical Chemistry, University of Oulu, Oulu, Finland
14Nordlab Oulu, Oulu University Hospital, Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: Elsevier, 2019
Publish Date: 2020-03-19


Purpose: Next-generation sequencing (NGS) has made genetic testing of patients with epileptic encephalopathies easier — novel variants are discovered and new phenotypes described. Variants in the same gene — even the same variant — can cause different types of epilepsy and neurodevelopmental disorders. Our aim was to identify the genetic causes of epileptic encephalopathies in paediatric patients with complex phenotypes.

Methods: NGS was carried out for three patients with epileptic encephalopathies. Detailed clinical features, brain magnetic resonance imaging and electroencephalography were analysed. We searched the Human Gene Mutation Database for the published GABRG2 variants with clinical description of patients and composed a summary of the variants and their phenotypic features.

Results: We identified two novel de novo GABRG2 variants, p.P282T and p.S306F, with new phenotypes including neuroradiological evidence of neurodegeneration and epilepsy of infancy with migrating focal seizures (EIMFS). One patient carried previously reported p.P83S variant with autism spectrum disorder (ASD) phenotype that has not yet been described related to GABRG2 disorders and a more severe epilepsy phenotype than reported earlier. In all, the literature search yielded twenty-two articles describing 27 different variants that were divided into two categories: those with self-limiting epilepsies and febrile seizures and those with more severe drug-resistant epileptic encephalopathies.

Conclusion: This study further expands the genotypic and phenotypic spectrum of epilepsies associated with GABRG2 variants. More knowledge is still needed about the influence of the environment, genetic background and other epilepsy susceptibility genes on the phenotype of the specific GABRG2 variants.

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Series: Seizure
ISSN: 1059-1311
ISSN-E: 1532-2688
ISSN-L: 1059-1311
Volume: 69
Pages: 99 - 104
DOI: 10.1016/j.seizure.2019.03.010
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This work was supported by the Alma and K.A. Snellman Foundation, Oulu, Finland; the Pediatric Research Foundation, Finland; The Finnish Cultural Foundation, the North Ostrobothnia Regional Fund, Oulu, Finland (grant number 60152194, 2015); Arvo ja Lea Ylppö Säätiö, Helsinki, Finland and Special State Grants for Health Research in Department of Pediatrics and Adolescence, Oulu University Hospital, Finland. Pohjois-Suomen Terveydenhuollon Tukisäätiö, Oulu, Finland.
Copyright information: © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license