This report describes mitochondrial complex III deficiency, nuclear type 2, a severe neurodegenerative disorder that is inherited as an autosomal recessive. The human gene implicated in this disease is TTC19, a nuclear-encoded subunit of mitochondrial respiratory chain complex III. There is a single fly ortholog, Dmel\Ttc19, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human TTC19 gene has not been introduced into flies.
One of the phenotypes described for Dmel\Ttc19 is bang-sensitivity (FBcv:0000391), a phenotype similar to seizure sensitivity in humans; see the human disease model report for epilepsy (FBhh0000268). Several other fly genes characterized as models of mitochondrial disease also exhibit bang-sensitive phenotypes, including sesB (see mitochondrial myopathy, SLC25A4(ANT1)-related, FBhh0000372), mt:ND2 (see mitochondrial complex I deficiency, MT-ND2-related, FBhh0000382), and mt:ATPase6 (see mitochondrial complex V disorders, MT-ATP6-related, FBhh0000376).
Adult flies homozygous for a loss-of-function Dmel\Ttc19 allele show strong bang sensitivity, severely reduced spontaneous motor activity, impaired response in an optomotor test, and reduced lifespan. The complex III activity is markedly reduced in mutant flies; complex I and complex IV activities are normal. Experiments in Drosophila supported work postulating a role of human TTC19 in mitochondrial function (FBrf0213121).
[updated Aug. 2016 by FlyBase; FBrf0222196]
Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001, pubmed:11528392; De Meirleir et al., 2003, oubmed:12910490 ). [from MIM:124000; 2021.09.26]
[MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 2; MC3DN2](https://omim.org/entry/615157)
[TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 19; TTC19](https://omim.org/entry/613814)
Mitochondrial complex III deficiency nuclear type 2 (MC3DN2) is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain [from MIM:615157; 2016.08.15]
Mitochondrial complex III deficiency nuclear type 2 (MC3DN2) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded TTC19 gene. [from MIM:615157; 2016.08.15]
TTC19 (tetratricopeptide repeat domain 19) is a subunit of mitochondrial respiratory chain complex III, which transfers electrons from coenzyme Q to cytochrome c. [from MIM:613814; 2016.08.15]
One to one (1 human to 1 Drosophila).
Moderate-scoring ortholog of human TTC19 (1 Drosophila to 1 human). Dmel\Ttc19 shares 25% identity and 43% similarity with the human gene.
