, Volume 32, Issue 2, pp 143-158
Date: 27 Dec 2008

Clinical and molecular features of mitochondrial DNA depletion syndromes

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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-γA (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.

Communicating editor: Gary Brown
Competing interests: None declared
References to electronic databases: MDS myopathic form: OMIM #609560. MDS encephalomyopathic form: OMIM #612073. MDS, encephalomyopathic form, with renal tubulopathy: OMIM #612075. MDS hepatocerebral form: OMIM #251880.
Presented at the Annual Symposium of the SSIEM, Lisbon, Portugal, 2–5 September 2008