Details of Disease

General Information of Disease (ID: DIS9SA7V)

• Disease Name: Mitochondrial myopathy
• Synonyms: mitochondrial myopathy; mitochondrial cytopathy
• Disease Class: 8C73: Mitochondrial myopathy
• Definition: Myopathy caused by mitochondrial abnormalities.
• Disease Hierarchy:
  DISP5E0H: Inborn mitochondrial metabolism disorder
  DISZ9JP4: Congenital structural myopathy
  DISOWG27: Myopathy
  DIS9SA7V: Mitochondrial myopathy
• ICD Code:
  ICD-11: ICD-11: 8C73
  ICD-10: ICD-10: G71.3
  Expand ICD-11: '8C73
  Expand ICD-10: 'G71.3
• Disease Identifiers:
  MONDO ID: MONDO_0009637
  MESH ID: D017240
  UMLS CUI: C0162670
  MedGen ID: 56484
  HPO ID: HP:0003737
  Orphanet ID: 206966
  SNOMED CT ID: 16851005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Bendavia	DMK43ON	Phase 3	NA	[1]
Nicotinamide riboside	DMJBYSE	Phase 1	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CS	TTZA6B3	Limited	Biomarker	[2]
GAA	TTLPC70	Limited	Biomarker	[3]
MYH7	TTNIMDP	Limited	Genetic Variation	[4]
PPID	TTNAFOU	Limited	Altered Expression	[5]
PPIF	TTRFQTB	Limited	Altered Expression	[5]
SLC25A4	TTU5A6Q	Limited	Genetic Variation	[6]
FGF21	TTQ916P	Strong	Biomarker	[7]
GDF15	TT4MXVG	Strong	Biomarker	[8]
IL1A	TTPM6HI	Strong	Biomarker	[9]
OPA1	TTTU49Q	Strong	Genetic Variation	[10]
TYMP	TTO0IB8	Strong	Biomarker	[11]
TYRP1	TTFRV98	Strong	Genetic Variation	[12]
VDAC1	TTAMKGB	Strong	Biomarker	[13]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A5	DTL1TRY	Limited	Genetic Variation	[14]
SLC25A21	DT2UQYR	Strong	Genetic Variation	[15]
SLC25A42	DTU4HKJ	Strong	Biomarker	[16]

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
IFI30	OT9DERT1	Limited	Biomarker	[17]
MIEF2	OT7VB4AM	Limited	Genetic Variation	[18]
NFU1	OTL58QZS	Limited	Genetic Variation	[19]
PERM1	OTZJW04C	Limited	Biomarker	[20]
PRPF6	OT3U0ABN	Limited	Genetic Variation	[14]
SARS2	OTU4T99W	Limited	Genetic Variation	[21]
TK2	OTS1V4XB	Limited	Genetic Variation	[22]
TMEM65	OT2JUZ7Q	Limited	Genetic Variation	[23]
TMEM70	OTLTKYXG	Limited	Genetic Variation	[24]
ADCK2	OTWTAQLU	moderate	Biomarker	[25]
CAMKMT	OTLJBRUW	moderate	Biomarker	[26]
NDUFA1	OTKBUQXP	moderate	Genetic Variation	[27]
ATP6	OTPHOGLX	Strong	Genetic Variation	[28]
COX1	OTG3O9BN	Strong	Genetic Variation	[29]
COX2	OTTMVBJJ	Strong	Genetic Variation	[30]
CYTB	OTAHB98A	Strong	Genetic Variation	[31]
DNA2	OT4DJFFU	Strong	Genetic Variation	[32]
FDX2	OT4KF6Q5	Strong	Genetic Variation	[33]
ISCU	OTSW6DQP	Strong	Genetic Variation	[19]
MPV17	OT579DMU	Strong	Genetic Variation	[34]
ND4	OT4RQVAA	Strong	Genetic Variation	[35]
NDUFV1	OTEVK4WW	Strong	Biomarker	[17]
POLG	OTDUCT04	Strong	Genetic Variation	[36]
PUS1	OTS2DQ0N	Strong	Genetic Variation	[37]
RRM2B	OTE8GBUR	Strong	Biomarker	[38]
TBPL1	OT4I143E	Strong	Genetic Variation	[12]
TFAM	OTXXV5V7	Strong	Biomarker	[39]
TIMM22	OTJMHX1V	Strong	Genetic Variation	[40]

References

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• [2] Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy.Brain. 2006 Dec;129(Pt 12):3402-12. doi: 10.1093/brain/awl149. Epub 2006 Jun 30.
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• [4] MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.Neurology. 2010 Aug 24;75(8):732-41. doi: 10.1212/WNL.0b013e3181eee4d5.
• [5] Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy.Hum Mol Genet. 2015 Dec 1;24(23):6580-7. doi: 10.1093/hmg/ddv361. Epub 2015 Sep 14.
• [6] Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number. Am J Hum Genet. 2016 Oct 6;99(4):860-876. doi: 10.1016/j.ajhg.2016.08.014. Epub 2016 Sep 29.
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• [8] Growth and differentiation factor 15 as a biomarker for mitochondrial myopathy.Mitochondrion. 2020 Jan;50:35-41. doi: 10.1016/j.mito.2019.10.005. Epub 2019 Oct 26.
• [9] Cytokine expression in the muscle of HIV-infected patients: evidence for interleukin-1 alpha accumulation in mitochondria of AZT fibers. Ann Neurol. 1994 Nov;36(5):752-8. doi: 10.1002/ana.410360511.
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• [12] Mitochondrial myopathy associated with a novel 5522G>A mutation in the mitochondrial tRNA(Trp) gene.Eur J Hum Genet. 2013 Aug;21(8):871-5. doi: 10.1038/ejhg.2012.272. Epub 2012 Dec 12.
• [13] Deficiency of the voltage-dependent anion channel: a novel cause of mitochondriopathy.Pediatr Res. 1996 May;39(5):760-5. doi: 10.1203/00006450-199605000-00003.
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• [15] Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease. Genet Med. 2018 Oct;20(10):1224-1235.
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• [17] Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100% antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon inducible protein (IP-30) precursor: is this a link between mitochondrial myopathy and inflammation?.Biochem Biophys Res Commun. 1998 Apr 17;245(2):599-606. doi: 10.1006/bbrc.1998.8486.
• [18] A novel mechanism causing imbalance of mitochondrial fusion and fission in human myopathies.Hum Mol Genet. 2018 Apr 1;27(7):1186-1195. doi: 10.1093/hmg/ddy033.
• [19] The presence of multiple cellular defects associated with a novel G50E iron-sulfur cluster scaffold protein (ISCU) mutation leads to development of mitochondrial myopathy.J Biol Chem. 2014 Apr 11;289(15):10359-10377. doi: 10.1074/jbc.M113.526665. Epub 2014 Feb 26.
• [20] Peroxisome proliferator-activated receptor coactivator 1 (PGC-1)- and estrogen-related receptor (ERR)-induced regulator in muscle 1 (Perm1) is a tissue-specific regulator of oxidative capacity in skeletal muscle cells.J Biol Chem. 2013 Aug 30;288(35):25207-25218. doi: 10.1074/jbc.M113.489674. Epub 2013 Jul 8.
• [21] Late-onset mitochondrial myopathy with dystrophic changes due to a G7497A mutation in the mitochondrial tRNA(Ser(UCN)) gene.Acta Neuropathol. 2005 Oct;110(4):426-30. doi: 10.1007/s00401-005-1063-z. Epub 2005 Aug 25.
• [22] Late-onset thymidine kinase 2 deficiency: a review of 18 cases.Orphanet J Rare Dis. 2019 May 6;14(1):100. doi: 10.1186/s13023-019-1071-z.
• [23] A mutation in the TMEM65 gene results in mitochondrial myopathy with severe neurological manifestations.Eur J Hum Genet. 2017 Jun;25(6):744-751. doi: 10.1038/ejhg.2017.20. Epub 2017 Mar 15.
• [24] Complex V TMEM70 deficiency results in mitochondrial nucleoid disorganization.Mitochondrion. 2011 Jan;11(1):191-9. doi: 10.1016/j.mito.2010.09.008. Epub 2010 Oct 30.
• [25] ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.J Clin Med. 2019 Sep 2;8(9):1374. doi: 10.3390/jcm8091374.
• [26] Calmodulin Methyltransferase Is Required for Growth, Muscle Strength, Somatosensory Development and Brain Function.PLoS Genet. 2015 Aug 6;11(8):e1005388. doi: 10.1371/journal.pgen.1005388. eCollection 2015 Aug.
• [27] Intragenic inversion of mtDNA: a new type of pathogenic mutation in a patient with mitochondrial myopathy. Am J Hum Genet. 2000 Jun;66(6):1900-4. doi: 10.1086/302927. Epub 2000 Apr 17.
• [28] Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography.Nucleic Acids Res. 2000 Oct 15;28(20):E89. doi: 10.1093/nar/28.20.e89.
• [29] Mitochondrial myopathy and rhabdomyolysis associated with a novel nonsense mutation in the gene encoding cytochrome c oxidase subunit I.J Neuropathol Exp Neurol. 2005 Feb;64(2):123-8. doi: 10.1093/jnen/64.2.123.
• [30] A novel MT-CO2 m.8249G>A pathogenic variation and the MT-TW m.5521G>A mutation in patients with mitochondrial myopathy.Mitochondrial DNA. 2014 Oct;25(5):394-9. doi: 10.3109/19401736.2013.803086. Epub 2013 Jul 10.
• [31] A novel mutation in the mitochondrial DNA cytochrome b gene (MTCYB) in a patient with Prader Willi syndrome.J Child Neurol. 2015 Mar;30(3):378-81. doi: 10.1177/0883073814530499. Epub 2014 Apr 25.
• [32] Novel mutations in DNA2 associated with myopathy and mtDNA instability.Ann Clin Transl Neurol. 2019 Sep;6(9):1893-1899. doi: 10.1002/acn3.50888. Epub 2019 Sep 2.
• [33] A novel complex neurological phenotype due to a homozygous mutation in FDX2.Brain. 2018 Aug 1;141(8):2289-2298. doi: 10.1093/brain/awy172.
• [34] Mitochondrial myopathies.Curr Opin Rheumatol. 2006 Nov;18(6):636-41. doi: 10.1097/01.bor.0000245729.17759.f2.
• [35] Mitochondrial DNA deletions in inclusion body myositis.Brain. 1993 Apr;116 ( Pt 2):325-36. doi: 10.1093/brain/116.2.325.
• [36] POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria.Gene. 2012 May 10;499(1):209-12. doi: 10.1016/j.gene.2012.02.034. Epub 2012 Mar 3.
• [37] Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA).Am J Hum Genet. 2004 Jun;74(6):1303-8. doi: 10.1086/421530. Epub 2004 Apr 22.
• [38] A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.Neuromuscul Disord. 2009 Feb;19(2):147-50. doi: 10.1016/j.nmd.2008.11.014. Epub 2009 Jan 12.
• [39] Increased mitochondrial Ca2+ and decreased sarcoplasmic reticulum Ca2+ in mitochondrial myopathy.Hum Mol Genet. 2009 Jan 15;18(2):278-88. doi: 10.1093/hmg/ddn355. Epub 2008 Oct 22.
• [40] Mutations of the mitochondrial carrier translocase channel subunit TIM22 cause early-onset mitochondrial myopathy. Hum Mol Genet. 2018 Dec 1;27(23):4135-4144. doi: 10.1093/hmg/ddy305.