De novo variants in neurodevelopmental disorders with epilepsy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10377746" target="_blank" >RIV/00216208:11130/18:10377746 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/18:10377746

Výsledek na webu

<a href="https://doi.org/10.1038/s41588-018-0143-7" target="_blank" >https://doi.org/10.1038/s41588-018-0143-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-018-0143-7" target="_blank" >10.1038/s41588-018-0143-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

De novo variants in neurodevelopmental disorders with epilepsy

Popis výsledku v původním jazyce

Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent-offspring trios ascertained to have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy, we identified 33 genes with a significant excess of DNVs, of which SNAP25 and GABRB2 had previously only limited evidence of disease association. Joint analysis of all individuals with NDDs also implicated CACNA1E as a novel disease-associated gene. Comparing NDDs with and without epilepsy, we found missense DNVs, DNVs in specific genes, age of recruitment, and severity of intellectual disability to be associated with epilepsy. We further demonstrate the extent to which our results affect current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDDs with epilepsy.

Název v anglickém jazyce

De novo variants in neurodevelopmental disorders with epilepsy

Popis výsledku anglicky

Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent-offspring trios ascertained to have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy, we identified 33 genes with a significant excess of DNVs, of which SNAP25 and GABRB2 had previously only limited evidence of disease association. Joint analysis of all individuals with NDDs also implicated CACNA1E as a novel disease-associated gene. Comparing NDDs with and without epilepsy, we found missense DNVs, DNVs in specific genes, age of recruitment, and severity of intellectual disability to be associated with epilepsy. We further demonstrate the extent to which our results affect current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDDs with epilepsy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Nature Genetics

ISSN

1061-4036

e-ISSN

—

Svazek periodika

50

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

1048-1053

Kód UT WoS článku

000437224400020

EID výsledku v databázi Scopus

2-s2.0-85049011462