Loss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies
Johanna Krüger, Julian Schubert, Josua Kegele, Audrey Labalme, Miaomiao Mao, Jacqueline Heighway, Guiscard Seebohm, Pu Yan, Mahmoud Koko, Kezban Aslan, Hande Çağlayan, Bernhard J. Steinhoff, Yvonne Weber, Pascale Kéo‐Kosal, Samuel F. Berkovic, Michael S. Hildebrand, Steven Petrou, Roland Krause, Patrick May, Gaëtan Lesca, Snezana Maljevic, Holger Lerche
Abstract
BACKGROUND: 7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. METHODS: 1292 families with GGE were studied by next-generation sequencing. Whole-cell patch-clamp recordings, biotinylation and phospholipid overlay assays were performed in mammalian cells combined with homology modelling. FINDINGS: -interaction. INTERPRETATION: 7.5-expressing neurons. Further studies on network level are necessary to understand which circuits are affected and how this induces generalized seizures. FUNDING: DFG/FNR Research Unit FOR-2715 (Germany/Luxemburg), BMBF rare disease network Treat-ION (Germany), foundation 'no epilep' (Germany).