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dc.contributor.authorEllard, Sian
dc.contributor.authorStals, Karen
dc.date.accessioned2021-06-15T12:31:18Z
dc.date.available2021-06-15T12:31:18Z
dc.date.issued2020-12-03
dc.identifier.citationBarish S et al. BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms. Am J Hum Genet. 2020 Dec 3;107(6):1096-1112. doi: 10.1016/j.ajhg.2020.11.003. Epub 2020 Nov 23.en_US
dc.identifier.pmid33232675
dc.identifier.doi10.1016/j.ajhg.2020.11.003
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621764
dc.description.abstractSWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.en_US
dc.language.isoenen_US
dc.publisherElsevier Scienceen_US
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0002-9297(20)30400-6en_US
dc.rights© 2020 American Society of Human Genetics.en_US
dc.subjectBAFopathyen_US
dc.subjectCG11873en_US
dc.subjectDrosophilaen_US
dc.subjectGLTSCR1en_US
dc.subjectchromatinen_US
dc.subjectdevelopmental delayen_US
dc.subjectintellectual disabilityen_US
dc.subjectncBAF complexen_US
dc.subjectposition effect variegationen_US
dc.subjectzebrafishen_US
dc.subjectWessex Classification Subject Headings::Biochemistryen_US
dc.titleBICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organismsen_US
dc.typeJournal Articleen_US
dc.identifier.journalAmerican Journal of Human Geneticsen_US
dc.identifier.pmcidPMC7820627
dc.description.fundingR24 OD022005/OD/NIH HHS/United States U01 HG007709/HG/NHGRI NIH HHS/United States U54 NS093793/NS/NINDS NIH HHS/United Statesen_US
dc.type.versionPublisheden_US
dc.description.admin-notepublished version, accepted version (6 month embargo), submitted versionen_US


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