This report describes oxoglutarate dehydrogenase deficiency (OGDHD); the human gene implicated in the disease is OGDH. OGDH encodes oxoglutarate dehydrogenase, one subunit of the 2-oxoglutarate dehydrogenase complex, which participates in the citric acid (TCA) cycle in the mitochondrial matrix. The most closely related gene in Drosophila is Dmel\Ogdh, for which multiple genetic reagents have been generated including RNAi-targeting constructs, overexpression constructs, a targeted CRISPR knockout construct, and alleles caused by insertional mutagenesis. Dmel\Ogdh is also orthologous to the human gene OGDHL.
Multiple UAS constructs of the human Hsap\OGDH gene have been introduced into flies, including wild-type and a variant implicated in this disease ( OGDH:p.Asn320Ser ). See the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) has been demonstrated for the Dmel\Ogdh lethal phenotype.
A severe loss-of-function mutation of Dmel\Ogdh causes lethality and neurophysiology defects. Using an eye-specific driver, RNAi directed against Ogdh results in age-progressive loss of synaptic transmission in photoreceptor cells. A variant analogous to the human OGDH:p.Asn320Ser variant has been generated and characterized.
See also the human disease model report 'Yoon-Bellen neurodevelopmental syndrome' (FBhh0000719).
[updated Apr. 2023 by FlyBase; FBrf0222196]
[OXOGLUTARATE DEHYDROGENASE DEFICIENCY; OGDHD](https://omim.org/entry/203740)
[OXOGLUTARATE DEHYDROGENASE; OGDH](https://omim.org/entry/613022)
Oxoglutarate dehydrogenase deficiency (OGDHD) is an autosomal recessive disorder associated with features of infantile- and pediatric-onset basal ganglia-associated movement disorders, hypotonia, developmental delays, ataxia, and seizures (summary by Yap et al., 2021; pubmed:32383294).
[from MIM:203740; 2022.01.09]
Oxoglutarate dehydrogenase deficiency (OGDHD) is caused by homozygous mutation in the oxoglutarate dehydrogenase gene (OGDH); one such family has been reported.[from MIM:203740; 2022.01.09]
OGDH and OGDHL are paralogous genes that share 77% identity and 87% similarity. [DIOPT; 2022.01.09]
OGDH encodes oxoglutarate dehydrogenase, one subunit of the 2-oxoglutarate dehydrogenase complex (OGDHC). The OGDHC functions primarily in the mitochondria, participating in the citric acid (TCA) cycle in the mitochondrial matrix. [from Gene Cards, OGDH; 2022.01.09]
Many to many: 2 human genes to 2 Drosophila genes.
High-scoring ortholog of human OGDH and OGDHL (2 Drosophila to 2 human). Dmel\Ogdh shares 56-62% identity and 68-75% similarity with the human genes.
