De novo SCN8A and inherited rare CACNA1H variants associated with severe developmental and epileptic encephalopathy
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články
PubMed
34399820
PubMed Central
PMC8365958
DOI
10.1186/s13041-021-00838-y
PII: 10.1186/s13041-021-00838-y
Knihovny.cz E-zdroje
- Klíčová slova
- CACNA1H, Calcium channel, Cav3.2 channel, Channelopathy, Encephalopathy, Epilepsy, Ion channels, Nav1.6 channel, SCN8A, Sodium channel,
- MeSH
- aktivační mutace MeSH
- bodová mutace MeSH
- duplikace genu MeSH
- epilepsie tonicko-klonická genetika MeSH
- gating iontového kanálu genetika fyziologie MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- missense mutace MeSH
- mnohočetné abnormality genetika MeSH
- napěťově řízený sodíkový kanál, typ 6 genetika fyziologie MeSH
- novorozenec MeSH
- refrakterní epilepsie genetika MeSH
- rodokmen MeSH
- skolióza genetika MeSH
- vápníkové kanály - typ T genetika fyziologie MeSH
- vývojové poruchy u dětí genetika MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CACNA1H protein, human MeSH Prohlížeč
- napěťově řízený sodíkový kanál, typ 6 MeSH
- SCN8A protein, human MeSH Prohlížeč
- vápníkové kanály - typ T MeSH
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.
Department of Pathophysiology 3rd Faculty of Medicine Charles University Prague Czech Republic
Department of Pediatric Neurology Mafraq Hospital Abu Dhabi United Arab Emirates
Department of Pediatrics Tawam Hospital Al Ain United Arab Emirates
Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic
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The T-type calcium channelosome
