title: Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients.
abstract: Mitochondrial DNA depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterised by a quantitative reduction of the mitochondrial DNA copy number. Three main clinical forms of MDS: myopathic, encephalomyopathic and hepatocerebral have been defined, although patients may present with other MDS associated clinical symptoms and signs that cover a wide spectrum of onset age and disease. We studied 52 paediatric individuals suspected to have MDS. These patients have been divided into three different groups, and the appropriate MDS genes have been screened according to their clinical and biochemical phenotypes. Mutational study of DGUOK, MPV17, SUCLA2, SUCLG1 and POLG allowed us to identify 3 novel mutations (c.1048G>A and c.1049G>T in SUCLA2 and c.531+4A>T in SUCLG1) and 7 already known mutations in 10 patients (8 families). Seventeen patients presented with mtDNA depletion in liver or muscle, but the cause of mtDNA depletion still remains unknown in 8 of them. When possible, we quantified mtDNA/nDNA and CS activity in the same tissue sample, providing an additional tool for the study of MDS. The ratio (mtDNA/nDNA)/CS has shed some light in the discrepant results between the mtDNA copy number and the enzymatic respiratory chain activities of some cases.
authors.affiliation: Division of Inborn Errors of Metabolism, Department of Biochemistry and Molecular Genetics, Hospital Clinic, Instituto de Investigación Biomédica Pi Sunyer, 08028 Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Navarro-Sastre
authors.forename: Frederic
authors.initials: F
authors.lastname: Tort
authors.forename: Judit
authors.initials: J
authors.lastname: Garcia-Villoria
authors.forename: Mónica Ruiz
authors.initials: MR
authors.lastname: Pons
authors.forename: Andrés
authors.initials: A
authors.lastname: Nascimento
authors.forename: Jaume
authors.initials: J
authors.lastname: Colomer
authors.forename: Jaume
authors.initials: J
authors.lastname: Campistol
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Yoldi
authors.forename: Ester
authors.initials: E
authors.lastname: López-Gallardo
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: Maria
authors.initials: M
authors.lastname: Unceta
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Martinez
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D000293:Adolescent; D002648:Child; D002950:Citrate (si)-Synthase / Q000235:genetics; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D009135:Muscular Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D013389:Succinate-CoA Ligases / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D002950:Citrate (si)-Synthase; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D013389:Succinate-CoA Ligases; C518788:SUCLA2 protein, human