English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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 Na v 1.6 voltage-gated sodium and Ca v 3.2 voltage-gated calcium channels, respectively. In vitro functional analysis of human Na v 1.6 and Ca v 3.2 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.   Supplementary Information  The online version contains supplementary material available at 10.1186/s13041-021-00838-y.

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