Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10505155" target="_blank" >RIV/00064203:_____/25:10505155 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/25:10505155
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=~yAOdnLJLr" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=~yAOdnLJLr</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-025-64838-5" target="_blank" >10.1038/s41467-025-64838-5</a>
Alternative languages
Result language
angličtina
Original language name
Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition
Original language description
Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SMARCA5 or SMARCA1 ISWI-chromatin remodeling enzyme. Pathogenic variants in BPTF and SMARCA5 have been previously implicated in NDDs. Here, we describe 35 individuals from 26 families with de novo or maternally inherited variants in the X-linked SMARCA1 gene. This SMARCA1-related NDD is associated with a spectrum of involvement, including mild to severe ID/DD, delayed or regressive speech development, ASD features, facial dysmorphisms, and other variable features. Individuals carrying SMARCA1 truncating variants exhibit a mildly unique genome-wide DNA methylation profile and a high penetrance of macrocephaly. Genetic dissection of the NURF complex using Smarca1, Smarca5, and Bptf single and double mouse knockouts reveals the importance of NURF composition and dosage for proper forebrain development. We propose that genetic alterations affecting different NURF components, including SMARCA1, result in a NDD with a broad clinical spectrum.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
16
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
21
Pages from-to
9875
UT code for WoS article
001614242800006
EID of the result in the Scopus database
2-s2.0-105021290067