Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder
The result's identifiers
Result code in 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>
Alternative codes found
RIV/60076658:12310/25:43910322 RIV/60461373:22810/25:43933173 RIV/00064203:_____/25:10500479
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Genetics in Medicine
ISSN
1098-3600
e-ISSN
1530-0366
Volume of the periodical
27
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
101555
UT code for WoS article
001587480100001
EID of the result in the Scopus database
2-s2.0-105017402220