Nature Communications (Apr 2022)
Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies
- Nathan L. Absalom,
- Vivian W. Y. Liao,
- Katrine M. H. Johannesen,
- Elena Gardella,
- Julia Jacobs,
- Gaetan Lesca,
- Zeynep Gokce-Samar,
- Alexis Arzimanoglou,
- Shimriet Zeidler,
- Pasquale Striano,
- Pierre Meyer,
- Ira Benkel-Herrenbrueck,
- Inger-Lise Mero,
- Jutta Rummel,
- Mary Chebib,
- Rikke S. Møller,
- Philip K. Ahring
Affiliations
- Nathan L. Absalom
- Brain and Mind Centre, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney
- Vivian W. Y. Liao
- Brain and Mind Centre, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney
- Katrine M. H. Johannesen
- Department of Epilepsy Genetics and Personalized Treatment, Member of the ERN EpiCARE, The Danish Epilepsy Centre
- Elena Gardella
- Department of Epilepsy Genetics and Personalized Treatment, Member of the ERN EpiCARE, The Danish Epilepsy Centre
- Julia Jacobs
- Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg
- Gaetan Lesca
- Department of Medical Genetics, Member of the ERN EpiCARE, University Hospitals of Lyon (HCL)
- Zeynep Gokce-Samar
- Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, Member of the ERN EpiCARE, University Hospitals of Lyon (HCL)
- Alexis Arzimanoglou
- Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, Member of the ERN EpiCARE, University Hospitals of Lyon (HCL)
- Shimriet Zeidler
- Department of Clinical Genetics, Erasmus MC
- Pasquale Striano
- IRCCS Institute “Giannina Gaslini”
- Pierre Meyer
- Pediatric Neurology Department, Phymedexp, Montpellier University, Inserm, CRNS, Montpellier University Hospital
- Ira Benkel-Herrenbrueck
- Sana-Krankenhaus Düsseldorf-Gerresheim, Academic Teaching Hospital der Heinrich-Heine-University Düsseldorf
- Inger-Lise Mero
- Department of Medical Genetics, Oslo University Hospital
- Jutta Rummel
- Department of Neurohabilitation, Oslo University Hospital
- Mary Chebib
- Brain and Mind Centre, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney
- Rikke S. Møller
- Department of Epilepsy Genetics and Personalized Treatment, Member of the ERN EpiCARE, The Danish Epilepsy Centre
- Philip K. Ahring
- Brain and Mind Centre, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney
- DOI
- https://doi.org/10.1038/s41467-022-29280-x
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 15
Abstract
Genetic variants of γ-aminobutyric acid (GABAA) receptors are associated with early onset epilepsies. Here, the authors show that functional loss or gain-of-function defines clinical outcomes, with gain-of-function variants unexpectedly more severe.
