Details of Disease | DrugMAP

General Information of Disease (ID: DISX4ATI)

Disease Name	Progressive external ophthalmoplegia
Synonyms	chronic progressive external ophthalmoplegia; progressive external ophthalmoplegia; chronic progressive external ophthalmoplegia [ambiguous]
Definition	A mitochondrial myopathy characterized by slowly progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. Ragged-red fibers and atrophy are found on muscle biopsy. Familial and sporadic forms may occur. Disease onset is usually in the first or second decade of life, and the illness slowly progresses until usually all ocular motility is lost. (From Adams et al., Principles of Neurology, 6th ed, p1422)
Disease Hierarchy	DIS9SA7V: Mitochondrial myopathy DISX4ATI: Progressive external ophthalmoplegia
Disease Identifiers	MONDO ID MONDO_0005181 MESH ID D017246 UMLS CUI C0162674 MedGen ID 102439 HPO ID HP:0000590 Orphanet ID 520820 SNOMED CT ID 46252003

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TYMP	TTO0IB8	Limited	Biomarker	[1]
C1QBP	TTWTD7F	moderate	Biomarker	[2]
SLC25A4	TTU5A6Q	moderate	Genetic Variation	[3]
SOD1	TTP9K3Q	moderate	Biomarker	[4]
SOD2	TT9O4C5	moderate	Biomarker	[5]
IL1A	TTPM6HI	Strong	Biomarker	[6]
NPTX2	TTNJ5A6	Strong	Biomarker	[1]
OPA1	TTTU49Q	Strong	Genetic Variation	[7]
MAPKAP1	TTWDKCL	Definitive	Genetic Variation	[8]
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⏷ Show the Full List of 9 DTT(s)

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PRPF6	OT3U0ABN	Limited	Genetic Variation	[3]
DGUOK	OT78HUZB	moderate	Genetic Variation	[9]
TOP3A	OT3CKUI9	moderate	Genetic Variation	[10]
CHMP1B	OTP715L8	Strong	Genetic Variation	[11]
POLG2	OTDBMZJB	Strong	Genetic Variation	[12]
RRM2B	OTE8GBUR	Strong	Genetic Variation	[13]
TK2	OTS1V4XB	Strong	Genetic Variation	[14]
AFG3L2	OTRPMAUX	Definitive	Genetic Variation	[15]
POLRMT	OT5Q8ZUJ	Definitive	Genetic Variation	[16]
PRIMPOL	OTVK6K9J	Definitive	Genetic Variation	[17]
RPTOR	OT4TQZ9F	Definitive	Genetic Variation	[8]
TNPO1	OT7W2CM8	Definitive	Genetic Variation	[8]
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⏷ Show the Full List of 12 DOT(s)

References

1	Muscle pain in mitochondrial diseases: a picture from the Italian network.J Neurol. 2019 Apr;266(4):953-959. doi: 10.1007/s00415-019-09219-x. Epub 2019 Feb 2.
2	Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies. Am J Hum Genet. 2017 Oct 5;101(4):525-538. doi: 10.1016/j.ajhg.2017.08.015. Epub 2017 Sep 21.
3	Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder.Mol Psychiatry. 2018 Oct;23(10):2039-2049. doi: 10.1038/s41380-018-0074-9. Epub 2018 Jun 11.
4	Antioxidant agents have a different expression pattern in muscle fibers of patients with mitochondrial diseases.Acta Neuropathol. 2002 Mar;103(3):215-20. doi: 10.1007/s004010100455. Epub 2001 Nov 16.
5	Increased expression of manganese-superoxide dismutase in fibroblasts of patients with CPEO syndrome.Mol Genet Metab. 2003 Nov;80(3):321-9. doi: 10.1016/j.ymgme.2003.08.005.
6	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.
7	Syndromic parkinsonism and dementia associated with OPA1 missense mutations.Ann Neurol. 2015 Jul;78(1):21-38. doi: 10.1002/ana.24410. Epub 2015 Jun 10.
8	Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase gamma associated with progressive external ophthalmoplegia.Hum Mol Genet. 2006 Jan 15;15(2):363-74. doi: 10.1093/hmg/ddi454. Epub 2005 Dec 20.
9	Alteration of nucleotide metabolism: a new mechanism for mitochondrial disorders.Clin Chem Lab Med. 2003 Jul;41(7):845-51. doi: 10.1515/CCLM.2003.128.
10	Topoisomerase 3 Is Required for Decatenation and Segregation of Human mtDNA. Mol Cell. 2018 Jan 4;69(1):9-23.e6. doi: 10.1016/j.molcel.2017.11.033. Epub 2017 Dec 28.
11	Mutation in TWINKLE in a Large Iranian Family with Progressive External Ophthalmoplegia, Myopathy, Dysphagia and Dysphonia, and Behavior Change.Arch Iran Med. 2016 Feb;19(2):87-91.
12	Whole exome sequencing identifies a homozygous POLG2 missense variant in an infant with fulminant hepatic failure and mitochondrial DNA depletion. Eur J Med Genet. 2016 Oct;59(10):540-5. doi: 10.1016/j.ejmg.2016.08.012. Epub 2016 Aug 31.
13	Novel mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging.Mitochondrion. 2016 Jan;26:81-5. doi: 10.1016/j.mito.2015.12.006. Epub 2015 Dec 12.
14	Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. Hum Mol Genet. 2012 Jan 1;21(1):66-75. doi: 10.1093/hmg/ddr438. Epub 2011 Sep 21.
15	Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28.JAMA Neurol. 2015 Jan;72(1):106-11. doi: 10.1001/jamaneurol.2014.1753.
16	Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia.Nat Struct Mol Biol. 2004 Aug;11(8):770-6. doi: 10.1038/nsmb805. Epub 2004 Jul 18.
17	A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms.Neurosci Res. 2020 Aug;157:58-63. doi: 10.1016/j.neures.2019.07.006. Epub 2019 Jul 23.