H01118 | |
H number | H01118 |
Name | Progressive external ophthalmoplegia; Autosomal dominant progressive external ophthalmoplegia |
Description | Progressive external ophthalmoplegia (PEO) is a progressive weakness of the external muscles of the eye resulting in blepharoptosis and ophthalmoparesis. Often other muscles are involved resulting in dysphagia and a variable neck and limb muscle weakness. Most sporadic PEO cases have an acquired genetic disease with a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in muscle. In familial PEO, several modes of inheritance occur. Patients may have a nuclear gene defect that predisposes to the accumulation of mtDNA deletions. Recently, mutations in such nuclear genes have been discovered. Some mutations are dominant (PEOA) and others recessive. |
Category | Nervous system disease |
Network | - |
Gene | (PEOA1) POLG [HSA:5428] [KO:K02332] (PEOA2) SLC25A4 [HSA:291] [KO:K05863] (PEOA3) TWNK [HSA:56652] [KO:K17680] (PEOA4) POLG2 [HSA:11232] [KO:K02333] (PEOA5) RRM2B [HSA:50484] [KO:K10808] (PEOA6) DNA2 [HSA:1763] [KO:K10742] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | - |
Comment | - |
Other DBs | ICD-11: 9C82.0 ICD-10: H49.4 MeSH: D017246 OMIM: 157640 609283 609286 610131 613077 615156 |
Reference | PMID:12835509 AUTHORS Van Goethem G, Martin JJ, Van Broeckhoven C TITLE Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA: unraveling the pathogenesis of human mitochondrial DNA instability and the initiation of a genetic classification. JOURNAL Neuromolecular Med 3:129-46 (2003) DOI:10.1385/NMM:3:3:129 PMID:22176657 AUTHORS Copeland WC TITLE Defects in mitochondrial DNA replication and human disease. JOURNAL Crit Rev Biochem Mol Biol 47:64-74 (2012) DOI:10.3109/10409238.2011.632763 PMID:12975295 (PEOA1) AUTHORS Filosto M, Mancuso M, Nishigaki Y, Pancrudo J, Harati Y, Gooch C, Mankodi A, Bayne L, Bonilla E, Shanske S, Hirano M, DiMauro S TITLE Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. JOURNAL Arch Neurol 60:1279-84 (2003) DOI:10.1001/archneur.60.9.1279 PMID:10926541 (PEOA2) AUTHORS Kaukonen J, Juselius JK, Tiranti V, Kyttala A, Zeviani M, Comi GP, Keranen S, Peltonen L, Suomalainen A TITLE Role of adenine nucleotide translocator 1 in mtDNA maintenance. JOURNAL Science 289:782-5 (2000) DOI:10.1126/science.289.5480.782 PMID:11431692 (PEOA3) AUTHORS Spelbrink JN, Li FY, Tiranti V, Nikali K, Yuan QP, Tariq M, Wanrooij S, Garrido N, Comi G, Morandi L, Santoro L, Toscano A, Fabrizi GM, Somer H, Croxen R, Beeson D, Poulton J, Suomalainen A, Jacobs HT, Zeviani M, Larsson C TITLE Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. JOURNAL Nat Genet 28:223-31 (2001) DOI:10.1038/90058 PMID:16685652 (PEOA4) AUTHORS Longley MJ, Clark S, Yu Wai Man C, Hudson G, Durham SE, Taylor RW, Nightingale S, Turnbull DM, Copeland WC, Chinnery PF TITLE Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. JOURNAL Am J Hum Genet 78:1026-34 (2006) DOI:10.1086/504303 PMID:19664747 (PEOA5) AUTHORS Tyynismaa H, Ylikallio E, Patel M, Molnar MJ, Haller RG, Suomalainen A TITLE A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. JOURNAL Am J Hum Genet 85:290-5 (2009) DOI:10.1016/j.ajhg.2009.07.009 PMID:23352259 (PEOA6) AUTHORS Ronchi D, Di Fonzo A, Lin W, Bordoni A, Liu C, Fassone E, Pagliarani S, Rizzuti M, Zheng L, Filosto M, Ferro MT, Ranieri M, Magri F, Peverelli L, Li H, Yuan YC, Corti S, Sciacco M, Moggio M, Bresolin N, Shen B, Comi GP TITLE Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability. JOURNAL Am J Hum Genet 92:293-300 (2013) DOI:10.1016/j.ajhg.2012.12.014 |