Human mutations in all three subunits of the mitochondrial ribonuclease P complex cause mitochondrial disease. This report describes HSD10 mitochondrial disease (HSD10MD), which is associated with the human gene HSD17B10 (also known as MRPP2). HSD10MD exhibits semi-dominant X-linked inheritance. There is a single orthologous gene in Drosophila, Dmel\scu, for which multiple genetic reagents have been generated, including loss-of-function mutations, RNAi-targeting constructs, overexpression constructs, and a CRISPR/Cas9-mediated knockout construct.
A UAS construct of the human Hsap\HSD17B10 gene has been introduced into flies, but has not been characterized in the context of this disease model.
Using tissue-specific RNAi knockdown, effects of reduced levels of Dmel\scu 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, but significant heart phenotypes (such as impaired contractility or arrhythmia) are not observed.
See also the FlyBase gene group report for MITOCHONDRIAL RNASE P COMPLEX (FBgg0001674).
[Updated Jun. 2022 by FlyBase; FBrf0222196]
[HSD10 MITOCHONDRIAL DISEASE; HSD10MD](https://omim.org/entry/300438)
[17-BETA-HYDROXYSTEROID DEHYDROGENASE X; HSD17B10](https://omim.org/entry/300256)
HSD10 mitochondrial disease (HSD10MD) most commonly presents as an X-linked neurodegenerative disorder with highly variable severity and age at onset ranging from the neonatal period to early childhood. The features are usually multisystemic, consistent with mitochondrial dysfunction. Some affected males have a severe infantile form associated with cardiomyopathy that may result in death in early childhood, whereas other rare patients may have juvenile onset or even atypical presentations with normal neurologic development. More severely affected males show developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation. Heterozygous females may show non-progressive developmental delay and intellectual disability, but may also be clinically normal. (Zschocke, 2012; pubmed:22127393).[from MIM:300438; 2022.06.14]
HSD10 mitochondrial disease (HSD10MD) is caused by hemizygous or heterozygous mutation in the HSD17B10 gene. [from MIM:300438; 2022.06.14]
HSD17B10 encodes 3-hydroxyacyl-CoA dehydrogenase type II, a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids; it is also 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, HSD17B10, TRMT10C; 2022.06.14]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human HSD17B10 (1 Drosophila to 1 human).
