De novo SCN8A and inherited rare CACNA1H variants associated with severe developmental and epileptic encephalopathy

0545025 - ÚOCHB 2022 RIV GB eng J - Článek v odborném periodiku
Stringer, Robin Nicholas - Jurkovicova-Tarabova, B. - Souza, I. A. - Ibrahim, J. - Vacík, T. - Fathalla, W. M. - Hertecant, J. - Zamponi, G. W. - Lacinová, L. - Weiss, Norbert
De novo SCN8A and inherited rare CACNA1H variants associated with severe developmental and epileptic encephalopathy.
Molecular Brain. Roč. 14, č. 1 (2021), č. článku 126. E-ISSN 1756-6606
Institucionální podpora: RVO:61388963
Klíčová slova: ion channels * channelopathy * calcium channel * CACNA1H * Ca(v)32 channel * sodium channel * SCN8A * Na(v)1.6 channel * epilepsy * encephalopathy
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.399, rok: 2021
Způsob publikování: Open access
https://doi.org/10.1186/s13041-021-00838-y

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that are characterized by seizures and developmental delay. DEEs are primarily attributed to genetic causes and an increasing number of cases have been correlated with variants in ion channel genes. In this study, we report a child with an early severe DEE. Whole exome sequencing showed a de novo heterozygous variant (c.4873–4881 duplication) in the SCN8A gene and an inherited heterozygous variant (c.952G > A) in the CACNA1H gene encoding for Nav1.6 voltage-gated sodium and Cav3.2 voltage-gated calcium channels, respectively. In vitro functional analysis of human Nav1.6 and Cav3.2 channel variants revealed mild but significant alterations of their gating properties that were in general consistent with a gain- and loss-of-channel function, respectively. Although additional studies will be required to confirm the actual pathogenic involvement of SCN8A and CACNA1H, these findings add to the notion that rare ion channel variants may contribute to the etiology of DEEs.
Trvalý link: http://hdl.handle.net/11104/0321802