HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F15%3A10295159" target="_blank" >RIV/00216208:11130/15:10295159 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00843989:_____/15:E0104815 RIV/00064203:_____/15:10295159

Výsledek na webu

<a href="http://dx.doi.org/10.1093/hmg/ddv083" target="_blank" >http://dx.doi.org/10.1093/hmg/ddv083</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/hmg/ddv083" target="_blank" >10.1093/hmg/ddv083</a>

Jazyk výsledku

angličtina

Název v původním jazyce

HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain

Popis výsledku v původním jazyce

Both gain- and loss-of-function mutations have recently implicated HCFC1 in neurodevelopmental disorders. Here, we extend our previous HCFC1 over-expression studies by employing short hairpin RNA to reduce the expression of Hcfc1 in embryonic neural cells. We show that in contrast to over-expression, loss of Hcfc1 favoured proliferation of neural progenitor cells at the expense of differentiation and promoted axonal growth of post-mitotic neurons. To further support the involvement of HCFC1 in neurological disorders, we report two novel HCFC1 missense variants found in individuals with intellectual disability (ID). One of these variants, together with three previously reported HCFC1 missense variants of unknown pathogenicity, were functionally assessedusing multiple cell-based assays. We show that three out of the four variants tested result in a partial loss of HCFC1 function. While over-expression of the wild-type HCFC1 caused reduction in HEK293T cell proliferation and axonal growt

Název v anglickém jazyce

HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain

Popis výsledku anglicky

Both gain- and loss-of-function mutations have recently implicated HCFC1 in neurodevelopmental disorders. Here, we extend our previous HCFC1 over-expression studies by employing short hairpin RNA to reduce the expression of Hcfc1 in embryonic neural cells. We show that in contrast to over-expression, loss of Hcfc1 favoured proliferation of neural progenitor cells at the expense of differentiation and promoted axonal growth of post-mitotic neurons. To further support the involvement of HCFC1 in neurological disorders, we report two novel HCFC1 missense variants found in individuals with intellectual disability (ID). One of these variants, together with three previously reported HCFC1 missense variants of unknown pathogenicity, were functionally assessedusing multiple cell-based assays. We show that three out of the four variants tested result in a partial loss of HCFC1 function. While over-expression of the wild-type HCFC1 caused reduction in HEK293T cell proliferation and axonal growt

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

<a href="/cs/project/NT14200" target="_blank" >NT14200: Identifikace genetických defektů v rodinách pacientů s autismem</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Human Molecular Genetics

ISSN

0964-6906

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

3335-3347

Kód UT WoS článku

000355674400004

EID výsledku v databázi Scopus

2-s2.0-84930445078