Résumé :
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Genetic alterations of the catalytic subunit of the polymerase gamma gene (POLG) have been recently involved in very diverse clinical diseases ranging from early severe Alpers-Huttenlocher syndrome to late adult diseases presenting with a very diverse combination of ophthalmoplegia, ataxia, epilepsy, peripheral neuropathy, gastro-intestinal symptoms, psychiatric disturbances, Parkinson syndrome... Polymerase gamma is the sole DNA polymerase that is responsible for the replication of mitochondrial DNA. The functional consequences of its alterations are defects of the mtDNA maintenance with either quantitative (depletion) or qualitative anomalies (mutations and deletions) of the mtDNA. These alterations are responsible for the defect in oxidative phosphorylation that underlies the onset of symptoms. The presence of mtDNA alterations is therefore an intrinsic part of the diagnostic criteria that lead to the search for POLG mutations. However, once created by the mutated POLG, qualitative mtDNA alterations have an evolution that is independent from the POLG mutation. They may be amplified as reported in normal ageing process. They also may be transmitted according to the maternal transmission of mtDNA and therefore independently from the POLG allele. We present two pedigrees that illustrate the questions raised by the co-existence of POLG and mtDNA mutations with respect to the relative responsibility of the mutations in the clinical presentation and the consequence on the mode of transmission of the symptoms.
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