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http://purl.uniprot.org/citations/36197437http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36197437http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

We aimed to investigate the molecular basis of a novel recognizable neurodevelopmental syndrome with scalp and enamel anomalies caused by truncating variants in the last exon of the gene FOSL2, encoding a subunit of the AP-1 complex.

Methods

Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker exchange. Gene expression in blood was analyzed using reverse transcription polymerase chain reaction. In vitro coimmunoprecipitation and proteasome inhibition assays in transfected HEK293 cells were performed to explore protein and AP-1 complex stability.

Results

We identified 11 individuals from 10 families with mostly de novo truncating FOSL2 variants sharing a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts. Mutant FOSL2 messenger RNAs escaped nonsense-mediated messenger RNA decay. Truncated FOSL2 interacts with c-JUN, thus mutated AP-1 complexes could be formed.

Conclusion

Truncating variants in the last exon of FOSL2 associate a distinct clinical phenotype by altering the regulatory degradation of the AP-1 complex. These findings reveal a new role for FOSL2 in human pathology."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.org/dc/terms/identifier"doi:10.1016/j.gim.2022.09.002"xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Carre W."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Devriendt K."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Brewer C."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Isidor B."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Moens L."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Odent S."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Besnard T."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Wuyts W."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Lapunzina P."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Gener B."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Cogne B."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Ruiz-Perez V.L."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Faoucher M."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Pasquier L."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Dubourg C."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Scalais E."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Perez-Jurado L.A."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Van Den Bogaert K."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Bailleul-Forestier I."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Meyts I."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Rivera-Barahona A."xsd:string
http://purl.uniprot.org/citations/36197437http://purl.uniprot.org/core/author"Rollier P."xsd:string
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