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

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dc.contributor.authorStringer, Robin N.
dc.contributor.authorJurkovicova-Tarabova, Bohumila
dc.contributor.authorSouza, Ivana A.
dc.contributor.authorIbrahim, Judy
dc.contributor.authorVacik, Tomas
dc.contributor.authorFathalla, Waseem M.
dc.contributor.authorHertecant, Jozef
dc.contributor.authorZamponi, Gerald W.
dc.contributor.authorLacinova, Lubica
dc.contributor.authorWeiss, Norbert
dc.date.accessioned2021-08-22T00:02:36Z
dc.date.available2021-08-22T00:02:36Z
dc.date.issued2021-08-16
dc.date.updated2021-08-22T00:02:36Z
dc.description.abstractAbstract 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.4873ā€“4881 duplication) in the SCN8A gene and an inherited heterozygous variant (c.952Gā€‰>ā€‰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.
dc.identifier.citationMolecular Brain. 2021 Aug 16;14(1):126
dc.identifier.doihttps://doi.org/10.1186/s13041-021-00838-y
dc.identifier.urihttp://hdl.handle.net/1880/113757
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.titleDe novo SCN8A and inherited rare CACNA1H variants associated with severe developmental and epileptic encephalopathy
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