{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mok JW"],"funding":["Foundation for the National Institutes of Health","National Health and Medical Research Council","National Institutes of Health Office of the Director","National Research Foundation of Korea","National Human Genome Research Institute","NIH HHS"],"pagination":["101429"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435177"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(7)"],"pubmed_abstract":["<h4>Purpose</h4>GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.<h4>Methods</h4>We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.<h4>Results</h4>Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented w"],"journal":["Genetics in medicine : official journal of the American College of Medical Genetics"],"pubmed_title":["C-terminal frameshift variants in GPKOW are associated with a multisystemic X-linked disorder."],"pmcid":["PMC12435177"],"funding_grant_id":["U54 OD030165","R24 OD031447","R24 OD022005"],"pubmed_authors":["Joubert M","Roth M","Kim SY","Rondeau S","Ketkar S","Rosenfeld JA","Posey JE","Mizerik E","Tran AA","Burrage LC","Cuinat S","Milosavljevic A","Heaney JD","Liu Z","Mok JW","Lee BH","Rogers J","Kearney D","Hanchard NA","Darshoori RZ","Valle Sirias F","Ramamurthy U","Yamamoto S","Lanza DG","Blazo M","Weisz-Hubshman M","Polak U","Kanca O","Nagamani SCS","Ramanathan V","Nizon M","Deb W","Machol K","Mao D","Wangler MF","Mackay L","Gecz J","Carroll R","Bellen HJ","Baylor College of Medicine Center for Precision Medicine Models"],"additional_accession":[]},"is_claimable":false,"name":"C-terminal frameshift variants in GPKOW are associated with a multisystemic X-linked disorder.","description":"<h4>Purpose</h4>GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.<h4>Methods</h4>We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.<h4>Results</h4>Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented w","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-04-08T19:32:15.241Z","creation":"2026-04-08T13:50:09.479Z"},"accession":"S-EPMC12435177","cross_references":{"pubmed":["40221893"],"doi":["10.1016/j.gim.2025.101429"]}}