{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yap ZY"],"funding":["NICHD NIH HHS","NHLBI NIH HHS","National Institutes of Health","Presbyterian Health Foundation","NIGMS NIH HHS","NIH HHS","CIHR"],"pagination":["388-400"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7647956"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(2)"],"pubmed_abstract":["2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in both OGDH protein and enzyme activity. Transfection of human OGDH c"],"journal":["Journal of inherited metabolic disease"],"pubmed_title":["A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease."],"pmcid":["PMC7647956"],"funding_grant_id":["R01 GM111084","P01‐HD087157","P20 GM103636","143325","R01‐GM111084","5 P20 GM103636‐07","R01HL125625","P01 HD087157","4411‐05‐07‐0","R01 HL125625","P40 OD018537"],"pubmed_authors":["Lee S","Matsuzaki S","Strucinska K","Si Y","Humphries K","Tarnopolsky MA","Yap ZY","Yoon WH"],"additional_accession":[]},"is_claimable":false,"name":"A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease.","description":"2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in both OGDH protein and enzyme activity. Transfection of human OGDH c","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-06-01T01:36:11.869Z","creation":"2022-02-10T09:58:26.755Z"},"accession":"S-EPMC7647956","cross_references":{"pubmed":["32383294"],"doi":["10.1002/jimd.12248"]}}