title: Clinical and molecular features of mitochondrial DNA depletion syndromes.
abstract: Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-gammaA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype-phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.
authors.affiliation: Unit of Molecular Neurogenetics, IRCCS Foundation Neurological Institute 'C. Besta', Via Temolo, 4, 20126, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Spinazzola
authors.forename: F
authors.initials: F
authors.lastname: Invernizzi
authors.forename: F
authors.initials: F
authors.lastname: Carrara
authors.forename: E
authors.initials: E
authors.lastname: Lamantea
authors.forename: A
authors.initials: A
authors.lastname: Donati
authors.forename: M
authors.initials: M
authors.lastname: Dirocco
authors.forename: I
authors.initials: I
authors.lastname: Giordano
authors.forename: M
authors.initials: M
authors.lastname: Meznaric-Petrusa
authors.forename: E
authors.initials: E
authors.lastname: Baruffini
authors.forename: I
authors.initials: I
authors.lastname: Ferrero
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D000140:Acidosis, Lactic / Q000209:etiology; D017668:Age of Onset; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000502:physiology; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; C105339:thymidine kinase 2; D013937:Thymidine Kinase