This report described mitochondrial DNA depletion syndrome 17 (MTDPS17); MTDPS17 exhibits autosomal recessive inheritance. Based on one reported case, the gene implicated in this disease is postulated to be MRM2, a nuclear gene involved in processing and modification of rRNA, including mitochondrial rRNA. There is a single orthologous gene in Drosophila, Mrm2. A small number of genetic reagent have been generated for Dmel\Mrm2 including RNAi-targeting constructs.
The human MRM2 gene has not been introduced into flies.
Ubiquitous knockdown of Dmel\Mrm2, effected by RNAi, typically results in lethality at the pupal state. Rare surviving adults lack normal mobility and exhibit anterior thoracic indentations, deformed wings, and flattened abdomen. The normal upregulation of mitochondrial respiratory chain components observed during the larval to adult transition is significantly reduced. Pan-neuronal knockdown of Dmel\Mrm2 also results in lethality. Muscle-specific knockdown allows survival to adulthood; adults exhibit significant locomotor defects.
[updated Feb. 2022 by FlyBase; FBrf0222196]
Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues without mutations or rearrangements in the mtDNA. MDS is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness, bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). [http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=35698.0 2016.11.23]
[MITOCHONDRIAL DNA DEPLETION SYNDROME 17; MTDPS17](https://omim.org/entry/618567)
[MITOCHONDRIAL RIBOSOMAL RNA METHYLTRANSFERASE 2; MRM2](https://omim.org/entry/606906)
One case has been described: a 7-year-old boy who presented at 8 months of life with developmental delay and a complex movement disorder characterized by generalized dyskinesia, featuring chorea and ballismus and also involving the cervical and oropharyngeal muscles, not responsive to levodopa and carbidopa treatment. [from MIM:618567; 2022.02.26]
Mitochondrial DNA depletion syndrome-17 (MTDPS17) is caused by homozygous mutation in the MRM2 gene. One such patient has been reported. [from MIM:618567; 2022.02.26]
Assessments after death of the patient: mitochondrial respiratory chain activities on muscle homogenate revealed multiple OXPHOS defects with complexes I and IV being severely affected, and other complexes at borderline level; quantitative PCR with DNA extracted from muscle revealed 40% of residual mtDNA copy number. [from MIM:618567; 2022.02.26]
MRM2 encodes a member of the S-adenosylmethionine-binding protein family that appears to be involved in processing and modification of rRNA, including mitochondrial rRNA. [Gene Cards, MRM2; 2022.02.26]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human MRM2 (1 Drosophila to 1 human).
