Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F25%3A10500479" target="_blank" >RIV/00216208:11130/25:10500479 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60076658:12310/25:43910322 RIV/60461373:22810/25:43933173 RIV/00064203:_____/25:10500479

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=zuQRROkqkX" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=zuQRROkqkX</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gim.2025.101555" target="_blank" >10.1016/j.gim.2025.101555</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder

Popis výsledku v původním jazyce

PURPOSE: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome, however no monogenic XPO1-related disorder has been described to date. MATERIALS AND METHODS: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We employed Drosophila to study XPO1 function in development and habituation learning. RESULTS: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants and half have coding variants (10 missense and 1 in-frame deletion variant). We find an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder (NDD). We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION: Our results establish XPO1 as a novel dominant monogenic NDD gene and demonstrate a central role for XPO1 in development.

Název v anglickém jazyce

Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder

Popis výsledku anglicky

PURPOSE: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome, however no monogenic XPO1-related disorder has been described to date. MATERIALS AND METHODS: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We employed Drosophila to study XPO1 function in development and habituation learning. RESULTS: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants and half have coding variants (10 missense and 1 in-frame deletion variant). We find an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder (NDD). We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION: Our results establish XPO1 as a novel dominant monogenic NDD gene and demonstrate a central role for XPO1 in development.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Genetics in Medicine

ISSN

1098-3600

e-ISSN

1530-0366

Svazek periodika

27

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

101555

Kód UT WoS článku

001587480100001

EID výsledku v databázi Scopus

2-s2.0-105017402220