| H00469 | |
| H number | H00469 |
| Name | Mitochondrial DNA depletion syndrome |
| Description | Mitochondrial DNA depletion syndromes (MDSs) are a group of heterogeneous autosomal recessive disorders associated with a severe reduction in mitochondrial DNA in the affected tissues. The manifestations vary from tissue-specific mtDNA depletion to wide-spread multisystemic disorders. Some genes are known to underlie this group of disorders, and many disease genes are still unidentified. However, the disease mechanisms seem to be intimately associated with mtDNA replication and nucleotide pool regulation. |
| Category | Inherited metabolic disorder, Mitochondrial disease |
| Network | nt06504(H00469) Base excision repair |
| Gene | (MTDPS1) TYMP [HSA:1890] [KO:K00758] (MTDPS2) TK2 [HSA:7084] [KO:K00857] (MTDPS3) DGUOK [HSA:1716] [KO:K00904] (MTDPS4A/4B) POLG [HSA:5428] [KO:K02332] (MTDPS5) SUCLA2 [HSA:8803] [KO:K01900] (MTDPS6) MPV17 [HSA:4358] [KO:K13348] (MTDPS7) TWNK [HSA:56652] [KO:K17680] (MTDPS8A/8B) RRM2B [HSA:50484] [KO:K10808] (MTDPS9) SUCLG1 [HSA:8802] [KO:K01899] (MTDPS10) AGK [HSA:55750] [KO:K09881] (MTDPS11) MGME1 [HSA:92667] [KO:K19465] (MTDPS12) SLC25A4 [HSA:291] [KO:K05863] (MTDPS13) FBXL4 [HSA:26235] [KO:K10270] (MTDPS14) OPA1 [HSA:4976] [KO:K17079] (MTDPS15) TFAM [HSA:7019] [KO:K11830] (MTDPS16) POLG2 [HSA:11232] [KO:K02333] (MTDPS17) MRM2 [HSA:29960] [KO:K02427] (MTDPS18) SLC25A21 [HSA:89874] [KO:K15110] (MTDPS19) SLC25A10 [HSA:1468] [KO:K13577] (MTDPS20) LIG3 [HSA:3980] [KO:K10776] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | MNGIE type: MTDPS1, MTDPS4B, MTDPS8B, MTDPS20 Myopathic type: MTDPS2, MTDPS11 Hepatocerebral type: MTDPS3, MTDPS6, MTDPS7, MTDPS15 Encephalomyopathic: MTDPS5, MTDPS8A, MTDPS9, MTDP12, MTDP13 Alpers type: MTDPS4A |
| Other DBs | ICD-11: 5C53.20 ICD-10: E88.8 MeSH: D017237 OMIM: 603041 609560 251880 203700 613662 612073 256810 271245 612075 245400 221350 615084 615418 615471 616896 617156 618528 618567 618811 618972 619780 |
| Reference | PMID:20444604 AUTHORS Suomalainen A, Isohanni P TITLE Mitochondrial DNA depletion syndromes--many genes, common mechanisms. JOURNAL Neuromuscul Disord 20:429-37 (2010) DOI:10.1016/j.nmd.2010.03.017 PMID:21855607 AUTHORS Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T TITLE Pyruvate therapy for mitochondrial DNA depletion syndrome. JOURNAL Biochim Biophys Acta 1820:632-6 (2012) DOI:10.1016/j.bbagen.2011.08.006 PMID:9924029 (MTDPS1) AUTHORS Nishino I, Spinazzola A, Hirano M TITLE Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. JOURNAL Science 283:689-92 (1999) DOI:10.1126/science.283.5402.689 PMID:11687801 (MTDPS2) AUTHORS Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O TITLE Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. JOURNAL Nat Genet 29:342-4 (2001) DOI:10.1038/ng751 PMID:11687800 (MTDPS3) AUTHORS Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, Shalata A, Anbinder Y, Berkowitz D, Hartman C, Barak M, Eriksson S, Cohen N TITLE The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. JOURNAL Nat Genet 29:337-41 (2001) DOI:10.1038/ng746 PMID:15122711 (MTDPS4A) AUTHORS Naviaux RK, Nguyen KV TITLE POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. JOURNAL Ann Neurol 55:706-12 (2004) DOI:10.1002/ana.20079 PMID:12825077 (MTDPS4B) AUTHORS Van Goethem G, Schwartz M, Lofgren A, Dermaut B, Van Broeckhoven C, Vissing J TITLE Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. JOURNAL Eur J Hum Genet 11:547-9 (2003) DOI:10.1038/sj.ejhg.5201002 PMID:15877282 (MTDPS5) AUTHORS Elpeleg O, Miller C, Hershkovitz E, Bitner-Glindzicz M, Bondi-Rubinstein G, Rahman S, Pagnamenta A, Eshhar S, Saada A TITLE Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. JOURNAL Am J Hum Genet 76:1081-6 (2005) DOI:10.1086/430843 PMID:16582910 (MTDPS6) AUTHORS Spinazzola A, Viscomi C, Fernandez-Vizarra E, Carrara F, D'Adamo P, Calvo S, Marsano RM, Donnini C, Weiher H, Strisciuglio P, Parini R, Sarzi E, Chan A, DiMauro S, Rotig A, Gasparini P, Ferrero I, Mootha VK, Tiranti V, Zeviani M TITLE MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. JOURNAL Nat Genet 38:570-5 (2006) DOI:10.1038/ng1765 PMID:16135556 (MTDPS7) AUTHORS Nikali K, Suomalainen A, Saharinen J, Kuokkanen M, Spelbrink JN, Lonnqvist T, Peltonen L TITLE Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. JOURNAL Hum Mol Genet 14:2981-90 (2005) DOI:10.1093/hmg/ddi328 PMID:17486094 (MTDPS8A) AUTHORS Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, Aubert S, Chretien D, de Lonlay P, Paquis-Flucklinger V, Arakawa H, Nakamura Y, Munnich A, Rotig A TITLE Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. JOURNAL Nat Genet 39:776-80 (2007) DOI:10.1038/ng2040 PMID:19667227 (MTDPS8B) AUTHORS Shaibani A, Shchelochkov OA, Zhang S, Katsonis P, Lichtarge O, Wong LJ, Shinawi M TITLE Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. JOURNAL Arch Neurol 66:1028-32 (2009) DOI:10.1001/archneurol.2009.139 PMID:17668387 (MTDPS9) AUTHORS Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F TITLE Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. JOURNAL Am J Hum Genet 81:383-7 (2007) DOI:10.1086/519222 PMID:22284826 (MTDPS10) AUTHORS Mayr JA, Haack TB, Graf E, Zimmermann FA, Wieland T, Haberberger B, Superti-Furga A, Kirschner J, Steinmann B, Baumgartner MR, Moroni I, Lamantea E, Zeviani M, Rodenburg RJ, Smeitink J, Strom TM, Meitinger T, Sperl W, Prokisch H TITLE Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. JOURNAL Am J Hum Genet 90:314-20 (2012) DOI:10.1016/j.ajhg.2011.12.005 PMID:23313956 (MTDPS11) AUTHORS Kornblum C, Nicholls TJ, Haack TB, Scholer S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H TITLE Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. JOURNAL Nat Genet 45:214-9 (2013) DOI:10.1038/ng.2501 PMID:16155110 (MTDPS12) AUTHORS Palmieri L, Alberio S, Pisano I, Lodi T, Meznaric-Petrusa M, Zidar J, Santoro A, Scarcia P, Fontanesi F, Lamantea E, Ferrero I, Zeviani M TITLE Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. JOURNAL Hum Mol Genet 14:3079-88 (2005) DOI:10.1093/hmg/ddi341 PMID:23993193 (MTDPS13) AUTHORS Bonnen PE, Yarham JW, Besse A, Wu P, Faqeih EA, Al-Asmari AM, Saleh MA, Eyaid W, Hadeel A, He L, Smith F, Yau S, Simcox EM, Miwa S, Donti T, Abu-Amero KK, Wong LJ, Craigen WJ, Graham BH, Scott KL, McFarland R, Taylor RW TITLE Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. JOURNAL Am J Hum Genet 93:471-81 (2013) DOI:10.1016/j.ajhg.2013.07.017 PMID:26561570 (MTDPS14) AUTHORS Spiegel R, Saada A, Flannery PJ, Burte F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, Shaag A, Mandel H, Schuler-Furman O, Shalev SA, Elpeleg O, Yu-Wai-Man P TITLE Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. JOURNAL J Med Genet 53:127-31 (2016) DOI:10.1136/jmedgenet-2015-103361 PMID:27448789 (MTDPS15) AUTHORS Stiles AR, Simon MT, Stover A, Eftekharian S, Khanlou N, Wang HL, Magaki S, Lee H, Partynski K, Dorrani N, Chang R, Martinez-Agosto JA, Abdenur JE TITLE Mutations in TFAM, encoding mitochondrial transcription factor A, cause neonatal liver failure associated with mtDNA depletion. JOURNAL Mol Genet Metab 119:91-9 (2016) DOI:10.1016/j.ymgme.2016.07.001 PMID:30157269 (MTDPS16) AUTHORS Hoff KE, DeBalsi KL, Sanchez-Quintero MJ, Longley MJ, Hirano M, Naini AB, Copeland WC TITLE Characterization of the human homozygous R182W POLG2 mutation in mitochondrial DNA depletion syndrome. JOURNAL PLoS One 13:e0203198 (2018) DOI:10.1371/journal.pone.0203198 PMID:28973171 (MTDPS17) AUTHORS Garone C, D'Souza AR, Dallabona C, Lodi T, Rebelo-Guiomar P, Rorbach J, Donati MA, Procopio E, Montomoli M, Guerrini R, Zeviani M, Calvo SE, Mootha VK, DiMauro S, Ferrero I, Minczuk M TITLE Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome. JOURNAL Hum Mol Genet 26:4257-4266 (2017) DOI:10.1093/hmg/ddx314 PMID:29517768 (MTDPS18) AUTHORS Boczonadi V, King MS, Smith AC, Olahova M, Bansagi B, Roos A, Eyassu F, Borchers C, Ramesh V, Lochmuller H, Polvikoski T, Whittaker RG, Pyle A, Griffin H, Taylor RW, Chinnery PF, Robinson AJ, Kunji ERS, Horvath R TITLE Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease. JOURNAL Genet Med 20:1224-1235 (2018) DOI:10.1038/gim.2017.251 PMID:29211846 (MTDPS19) AUTHORS Punzi G, Porcelli V, Ruggiu M, Hossain MF, Menga A, Scarcia P, Castegna A, Gorgoglione R, Pierri CL, Laera L, Lasorsa FM, Paradies E, Pisano I, Marobbio CMT, Lamantea E, Ghezzi D, Tiranti V, Giannattasio S, Donati MA, Guerrini R, Palmieri L, Palmieri F, De Grassi A TITLE SLC25A10 biallelic mutations in intractable epileptic encephalopathy with complex I deficiency. JOURNAL Hum Mol Genet 27:499-504 (2018) DOI:10.1093/hmg/ddx419 PMID:33855352 (MTDPS20) AUTHORS Bonora E, Chakrabarty S, Kellaris G, Tsutsumi M, Bianco F, Bergamini C, Ullah F, Isidori F, Liparulo I, Diquigiovanni C, Masin L, Rizzardi N, Cratere MG, Boschetti E, Papa V, Maresca A, Cenacchi G, Casadio R, Martelli P, Matera I, Ceccherini I, Fato R, Raiola G, Arrigo S, Signa S, Sementa AR, Severino M, Striano P, Fiorillo C, Goto T, Uchino S, Oyazato Y, Nakamura H, Mishra SK, Yeh YS, Kato T, Nozu K, Tanboon J, Morioka I, Nishino I, Toda T, Goto YI, Ohtake A, Kosaki K, Yamaguchi Y, Nonaka I, Iijima K, Mimaki M, Kurahashi H, Raams A, MacInnes A, Alders M, Engelen M, Linthorst G, de Koning T, den Dunnen W, Dijkstra G, van Spaendonck K, van Gent DC, Aronica EM, Picco P, Carelli V, Seri M, Katsanis N, Duijkers FAM, Taniguchi-Ikeda M, De Giorgio R TITLE Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy. JOURNAL Brain 144:1451-1466 (2021) DOI:10.1093/brain/awab056 |