{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["DiSanza BL"],"funding":["National Cancer Institute","National Institutes of Health","Chan Zuckerberg Initiative"],"pagination":["100525"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12670911"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["Branched-chain amino acid transaminase-1 (BCAT1) initiates the catabolism of branched-chain amino acids (BCAAs), which are essential for neurologic function. However, the role of BCAT1 in neurodevelopment is largely unknown. Here, we identify compound heterozygous BCAT1 variants in a patient with a severe progressive neurodevelopmental syndrome. To investigate the functional consequences, we established patient variant (BCAT1: c.792T>A p.Phe264Leu; c.1042G>A p.Glu348Lys) and BCAT1 knockout hiPSC models. Both disease models show profound defects in cortical neuron differentiation and neurite outgrowth. Furthermore, metabolic analysis revealed evidence of mitochondrial dysfunction associated with increased levels of tricarboxylic acid (TCA) cycle intermediates, glutamate, and glutamine. This"],"journal":["HGG advances"],"pubmed_title":["Bi-allelic variants in BCAT1 impair mitochondrial function and are associated with a candidate neurometabolic disorder."],"pmcid":["PMC12670911"],"funding_grant_id":["P30 CA016520","P30DK050306"],"pubmed_authors":["Sertori Finoti L","DiSanza BL","Helman GT","Skarnes WC","Bhoj EJ","Ramos-Rodriguez L","McDonough JA","Vanderver A","Ortiz-Gonzalez X","Ning G","Porcari GS","Pizzino A","Fagan G","Burris DM","Weiss E","Whitehead MT","Taft RJ","Ahrens-Nicklas RC","Waldman A","Simons C"],"additional_accession":[]},"is_claimable":false,"name":"Bi-allelic variants in BCAT1 impair mitochondrial function and are associated with a candidate neurometabolic disorder.","description":"Branched-chain amino acid transaminase-1 (BCAT1) initiates the catabolism of branched-chain amino acids (BCAAs), which are essential for neurologic function. However, the role of BCAT1 in neurodevelopment is largely unknown. Here, we identify compound heterozygous BCAT1 variants in a patient with a severe progressive neurodevelopmental syndrome. To investigate the functional consequences, we established patient variant (BCAT1: c.792T>A p.Phe264Leu; c.1042G>A p.Glu348Lys) and BCAT1 knockout hiPSC models. Both disease models show profound defects in cortical neuron differentiation and neurite outgrowth. Furthermore, metabolic analysis revealed evidence of mitochondrial dysfunction associated with increased levels of tricarboxylic acid (TCA) cycle intermediates, glutamate, and glutamine. This","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-11T04:46:26.426Z","creation":"2026-06-11T03:08:01.994Z"},"accession":"S-EPMC12670911","cross_references":{"pubmed":["41029903"],"doi":["10.1016/j.xhgg.2025.100525"]}}