biostudies-literatureWhittle EFNICHD NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)NINDS NIH HHSNIGMS NIH HHS100332https://www.ebi.ac.uk/biostudies/studies/S-EPMC9905285biostudies-literatureUnknown25(2)<h4>Purpose</h4>This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.<h4>Methods</h4>We performed a detailed clinical characterization of 4 unrelated individuals from consanguineous families with a neurodevelopmental disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, and functional analyses of variants in HEK293 cells and Drosophila melanogaster, as well as in proband-derived fibroblast cells.<h4>Results</h4>In the 4 individuals, we identified 3 novel homozygous variants in oxoglutarate dehydrogenase (OGDH) (NM_002541.3), which encodes a subunit of the tricarboxylic acid cycle enzyme α-ketoGenetics in medicine : official journal of the American College of Medical GeneticsBiallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.PMC9905285MR/S01165X/1P20 GM103636G0601943MR/N013638/1NIHR205088R01 NS121298MR/S005021/1P50 HD105354R01 GM142143Yang HLee SHoulden HIgnatius EBuhas DPittman AMKarimiani EGBadv RSChilian MKose MToosi MBGanetzky RDMaroofian RWhittle EFTorbati PNProgri HRahman SCarroll CJJamshidi YShelihan IElloumi HZYoon WHfalseBiallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.<h4>Purpose</h4>This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.<h4>Methods</h4>We performed a detailed clinical characterization of 4 unrelated individuals from consanguineous families with a neurodevelopmental disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, and functional analyses of variants in HEK293 cells and Drosophila melanogaster, as well as in proband-derived fibroblast cells.<h4>Results</h4>In the 4 individuals, we identified 3 novel homozygous variants in oxoglutarate dehydrogenase (OGDH) (NM_002541.3), which encodes a subunit of the tricarboxylic acid cycle enzyme α-keto2023-01-01T00:00:00Z2023 Feb2026-05-28T11:51:29.441Z2025-04-07T03:19:43.419ZS-EPMC99052853652015210.1016/j.gim.2022.11.001