Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies.
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ABSTRACT:
SUBMITTER: Absalom NL
PROVIDER: S-EPMC8983652 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies.
Absalom Nathan L NL Liao Vivian W Y VWY Johannesen Katrine M H KMH Gardella Elena E Jacobs Julia J Lesca Gaetan G Gokce-Samar Zeynep Z Arzimanoglou Alexis A Zeidler Shimriet S Striano Pasquale P Meyer Pierre P Benkel-Herrenbrueck Ira I Mero Inger-Lise IL Rummel Jutta J Chebib Mary M Møller Rikke S RS Ahring Philip K PK
Nature communications 20220405 1
Many patients with developmental and epileptic encephalopathies present with variants in genes coding for GABA<sub>A</sub> receptors. These variants are presumed to cause loss-of-function receptors leading to reduced neuronal GABAergic activity. Yet, patients with GABA<sub>A</sub> receptor variants have diverse clinical phenotypes and many are refractory to treatment despite the availability of drugs that enhance GABAergic activity. Here we show that 44 pathogenic GABRB3 missense variants segreg ...[more]
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