Pathologies liées à des mutations de l’ADN mitochondrial

Abstract

Mitochondrial diseases are common metabolic disorders characterized by a large clinical and genetic heterogeneity. The double genetic origin of mitochondria, nuclear DNA and mitochondrial DNA (mtDNA) and mitochondrial heteroplasmy defined by the coexistence of mutated and normal mitochondria within cells are at the origin of the complexity of the diagnosis of these diseases. The inheritance of mtDNA is exclusively maternal, segregating randomly during cell divisions. These mitochondrial diseases can occur at any age and the clinical presentations are extremely variable affecting high energy demand tissues such as muscle or brain but all organs are likely to be affected. Several hundred mutations of mtDNA could thus be identified responsible for mitochondrial diseases with different types of mutations of the mtDNA such as point mutations, deletions or mtDNA depletion. The recent development of high-throughput sequencing technologies has significantly improved the diagnosis of mitochondrial disorders allowing a systematic analysis of the mtDNA with greater sensitivity in the variant detection but revealed at the same time a greater complexity of the analysis and interpretation of the mtDNA variants with the need to develop new bioinformatics tools dedicated to mitochondrial genetics.