Human mutations in all three subunits of the mitochondrial ribonuclease P complex cause mitochondrial disease. This report describes combined oxidative phosphorylation deficiency 30 (COXPD30), which is associated with the human gene TRMT10C (also known as MRPP1). COXPD30 exhibits autosomal recessive inheritance. There is a single orthologous gene in Drosophila, Dmel\rswl, for which multiple genetic reagents have been generated, including amorphic mutations, RNAi-targeting and overexpression constructs, and a CRISPR/Cas9-mediated knockout construct.
The human TRMT10C gene has not been introduced into flies.
Using tissue-specific RNAi knockdown, effects of reduced levels of Dmel\rswl in skeletal and heart muscle have been assessed. Reduction in skeletal muscle decreases adult eclosion and causes reduced muscle mass and function; adult flies exhibit age-progressive locomotor defects. Reduction in cardiac muscle results in reduced adult lifespan and phenotypes of impaired contractility and significant arrhythmia in adult hearts.
See also the FlyBase gene group report for MITOCHONDRIAL RNASE P COMPLEX (FBgg0001674).
[Updated Jun. 2022 by FlyBase; FBrf0222196]
Combined oxidative phosphorylation deficiency is an autosomal recessive multisystem disorder with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation (OXPHOS) system. Onset occurs at or soon after birth, and features can include growth retardation, microcephaly, hypertonicity, axial hypotonia, encephalopathy, cardiomyopathy, and liver dysfunction. Death usually occurs in the first weeks or years of life (summary by Smits et al., 2011; pubmed:21119709). [from MIM:609060; 2021.04.17]
[COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 30; COXPD30](https://omim.org/entry/616974)
[tRNA METHYLTRANSFERASE 10C, MITOCHONDRIAL RNAse P SUBUNIT; TRMT10C](https://omim.org/entry/615423)
Metodiev et al. (2016, pubmed:27132592) reported 2 unrelated infants with a fatal systemic mitochondrial disease. The patients presented at birth with hypotonia, feeding difficulties, and deafness. One also had cardiac left ventricular hypertrophy and brain imaging suggestive of frontal polymicrogyria. Laboratory studies in both patients showed lactic acidosis, increased cerebrospinal fluid lactate levels, increased serum alanine, and abnormal liver function tests. Both infants died of respiratory failure at age 5 months. Patient skeletal muscle cells showed decreased activities of mitochondrial complexes I and IV in both patients, and decreased complex III activity in only 1 patient. Muscle biopsy, performed in 1 patient, showed COX-deficient ragged-red fibers. [from MIM:616974; 2022.06.14]
Combined oxidative phosphorylation deficiency-30 (COXPD30) is caused by homozygous or compound heterozygous mutation in the TRMT10C gene. [from MIM:616974; 2022.06.14]
TRMT10C encodes a mitochondrial tRNA N(1)-methyltransferase involved in mitochondrial tRNA maturation; a component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3, which cleaves tRNA molecules in their 5' ends. [Gene Cards, TRMT10C; 2022.06.14]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human TRMT10C (1 Drosophila to 1 human).
