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Syndromic forms of intellectual disability frequently have a genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components of TATA-binding protein associated factors (TAFs) have recently been identified in a subset of patients with intellectual disability, craniofacial hypoplasia, and congenital heart disease. This syndrome has been termed as a TAFopathy and includes mutations in TATA binding protein (TBP), TAF1, TAF2, and TAF6. The underlying mechanism by which TAFopathies give rise to neurodevelopmental, craniofacial, and cardiac abnormalities remains to be defined. Through a forward genetic screen in zebrafish, we have recovered a recessive mutant phenotype characterized by craniofacial hypoplasia, ventricular hypoplasia, heart failure at 96\u2005h post-fertilization and lethality, and show it is caused by a nonsense mutation in taf5. CRISPR\/CAS9 mediated gene editing revealed that these defects where phenocopied by mutations in taf1 and taf5. Mechanistically, taf5-\/- zebrafish displayed misregulation in metabolic gene expression and metabolism as evidenced by RNA sequencing, respiration assays, and metabolite studies. Collectively, these findings suggest that the TAF complex may contribute to neurologic, craniofacial, and cardiac development through regulation of metabolism.<\/jats:p>","DOI":"10.1242\/bio.059905","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T09:35:06Z","timestamp":1689240906000},"source":"Crossref","is-referenced-by-count":4,"title":["Deletion of <i>taf1<\/i> and <i>taf5<\/i> in zebrafish capitulate cardiac and craniofacial abnormalities associated with TAFopathies through perturbations in metabolism"],"prefix":"10.1242","volume":"12","author":[{"given":"Jamison","family":"Leid","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine 1 , Washington University School of Medicine, St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9668-6497","authenticated-orcid":false,"given":"Ryan","family":"Gray","sequence":"additional","affiliation":[{"name":"Dell Pediatrics Research Institute, University of Texas at Austin 2 Departments of Nutritional Sciences , , Austin, TX 78723 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rakita","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine 1 , Washington University School of Medicine, St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Koenig","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine 1 , Washington University School of Medicine, St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine 1 , Washington University School of Medicine, St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A. J.","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Washington University Center for Cellular Imaging, Washington University School of Medicine 3 Departments of Neuroscience and Cell Biology , , St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-1677","authenticated-orcid":false,"given":"Charles","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 4 Department of Developmental Biology , , St. Louis, MO 63110 , USA"},{"name":"Washington University School of Medicine 5 Division of Oncology, Department of Medicine , , St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilianna","family":"Solnica-Krezel","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 4 Department of Developmental Biology , , St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-9945","authenticated-orcid":false,"given":"Kory J.","family":"Lavine","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine 1 , Washington University School of Medicine, St. Louis, MO 63110 , USA"},{"name":"Washington University School of Medicine 4 Department of Developmental Biology , , St. Louis, MO 63110 , USA"},{"name":"Washington University School of Medicine 6 Department of Immunology and Pathology , , St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"2023081111534137900_BIO059905C1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/mds.28305","article-title":"TAF1 transcripts and neurofilament light chain as biomarkers for X-linked dystonia-parkinsonism","volume":"36","author":"Al Ali","year":"2021","journal-title":"Mov. 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