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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00545025" target="_blank" >RIV/61388963:_____/21:00545025 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/21:43921908 RIV/00216208:11110/21:10430282

Výsledek na webu

<a href="https://doi.org/10.1186/s13041-021-00838-y" target="_blank" >https://doi.org/10.1186/s13041-021-00838-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13041-021-00838-y" target="_blank" >10.1186/s13041-021-00838-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Brain

ISSN

1756-6606

e-ISSN

1756-6606

Svazek periodika

14

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

5

Strana od-do

126

Kód UT WoS článku

000686625300002

EID výsledku v databázi Scopus

2-s2.0-85112727757