1. Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients.
- Author
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Navarro-Sastre A, Tort F, Garcia-Villoria J, Pons MR, Nascimento A, Colomer J, Campistol J, Yoldi ME, López-Gallardo E, Montoya J, Unceta M, Martinez MJ, Briones P, and Ribes A
- Subjects
- Adolescent, Child, Citrate (si)-Synthase genetics, DNA Copy Number Variations, DNA Mutational Analysis, DNA Polymerase gamma, DNA, Mitochondrial genetics, DNA-Directed DNA Polymerase genetics, Diffuse Cerebral Sclerosis of Schilder diagnosis, Diffuse Cerebral Sclerosis of Schilder enzymology, Diffuse Cerebral Sclerosis of Schilder genetics, Female, Humans, Male, Metabolism, Inborn Errors diagnosis, Metabolism, Inborn Errors enzymology, Mitochondria enzymology, Mitochondria genetics, Mitochondrial Diseases diagnosis, Mitochondrial Diseases enzymology, Mitochondrial Myopathies diagnosis, Mitochondrial Myopathies enzymology, Muscular Diseases diagnosis, Muscular Diseases enzymology, Mutation, Phosphotransferases (Alcohol Group Acceptor) genetics, Young Adult, Metabolism, Inborn Errors genetics, Mitochondrial Diseases genetics, Mitochondrial Myopathies genetics, Muscular Diseases genetics, Succinate-CoA Ligases genetics
- 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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