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.
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Metabolic disorders
Inborn errors of metabolism
5C53 Inborn errors of energy metabolism
H00469 Mitochondrial DNA depletion syndrome
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06504 Base excision repair
H00469 Mitochondrial DNA depletion syndrome
Cellular process
nt06536 Mitophagy
H00469 Mitochondrial DNA depletion syndrome
Thompson K, Majd H, Dallabona C, Reinson K, King MS, Alston CL, He L, Lodi T, Jones SA, Fattal-Valevski A, Fraenkel ND, Saada A, Haham A, Isohanni P, Vara R, Barbosa IA, Simpson MA, Deshpande C, Puusepp S, Bonnen PE, Rodenburg RJ, Suomalainen A, Ounap K, Elpeleg O, Ferrero I, McFarland R, Kunji ER, Taylor RW
Title
Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.
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.
Dosekova P, Dubiel A, Karlowicz A, Zietkiewicz S, Rydzanicz M, Habalova V, Pienkowski VM, Skirkova M, Han V, Mosejova A, Gdovinova Z, Kaliszewska M, Tonska K, Szymanski MR, Skorvanek M, Ploski R
Title
Whole exome sequencing identifies a homozygous POLG2 missense variant in an adult patient presenting with optic atrophy, movement disorders, premature ovarian failure and mitochondrial DNA depletion.
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
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.
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
Brite
Human diseases in ICD-11 classification [BR:br08403]
09 Diseases of the visual system
Strabismus or ocular motility disorders
9C82 Disorders of extraocular muscles
H01118 Progressive external ophthalmoplegia
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06509 DNA replication
H01118 Progressive external ophthalmoplegia
nt06504 Base excision repair
H01118 Progressive external ophthalmoplegia
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.
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.
