{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li X"],"funding":["Genome Canada and Genome BC"],"pagination":["64"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480863"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Gamma-butyrobetaine hydroxylase (BBOX1) catalyses the last step of carnitine biosynthesis, converting γ-butyrobetaine (γ-BB) into L-carnitine. Here we show, for the first time, that biallelic variants in BBOX1 are associated with decreased levels of L-carnitine and increased plasma levels of γ-BB in three patients from two unrelated families presenting with myopathic, neurodevelopmental, and late-onset psychiatric manifestations. Using a knockout C. elegans model of BBOX1 homolog, gbh-1, and strains harboring patient-derived variants (gbh-1(D72G) for p.Asp59Gly, gbh-1(G283R) for p.Gly263Arg, and gbh-1(G247Vfs6) for p.Gly227Valfs*6), we show very low L-carnitine levels and significantly elevated γ-BB in c.675delA and c.787G>A mutants, and moderately elevated γ-BB in c.176A>G. Furthermore, w"],"journal":["NPJ genomic medicine"],"pubmed_title":["Biallelic variants in BBOX1 cause L-Carnitine deficiency and elevated γ-butyrobetaine."],"pmcid":["PMC12480863"],"funding_grant_id":["275SIL"],"pubmed_authors":["Horvath G","Li X","Rakic B","Mwenifumbo J","Stockler-Ipsiroglu S","Arbour L","Vaz FM","Lehman A","Tarailo-Graovac M","Jacob KJ","Yeganeh M","Sinclair G"],"additional_accession":[]},"is_claimable":false,"name":"Biallelic variants in BBOX1 cause L-Carnitine deficiency and elevated γ-butyrobetaine.","description":"Gamma-butyrobetaine hydroxylase (BBOX1) catalyses the last step of carnitine biosynthesis, converting γ-butyrobetaine (γ-BB) into L-carnitine. Here we show, for the first time, that biallelic variants in BBOX1 are associated with decreased levels of L-carnitine and increased plasma levels of γ-BB in three patients from two unrelated families presenting with myopathic, neurodevelopmental, and late-onset psychiatric manifestations. Using a knockout C. elegans model of BBOX1 homolog, gbh-1, and strains harboring patient-derived variants (gbh-1(D72G) for p.Asp59Gly, gbh-1(G283R) for p.Gly263Arg, and gbh-1(G247Vfs6) for p.Gly227Valfs*6), we show very low L-carnitine levels and significantly elevated γ-BB in c.675delA and c.787G>A mutants, and moderately elevated γ-BB in c.176A>G. Furthermore, w","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T23:09:41.308Z","creation":"2026-05-02T03:12:03.574Z"},"accession":"S-EPMC12480863","cross_references":{"pubmed":["41022783"],"doi":["10.1038/s41525-025-00523-2"]}}