SEARCHING FOR GENES AFFECTING THE STRUCTURAL INTEGRITY OF THE MITOCHONDRIAL GENOME

Mendelian traits associated with qualitative or quantitative abnormalities of mtDNA are presumably caused by mutations in nucleus-encoded genes that deleteriously interact with the mitochondrial genome. Qualitative abnormalities of mtDNA are typically represented by pleioplasmic multiple mtDNA deletions, that are detected in stable tissues, including skeletal muscle, of patients affected by Autosomal Dominant Chronic Progressive External Ophthalmoplegia. Quantitative abnormalities are represented by tissue-specific depletion of mtDNA, associated with different clinical presentations in infancy or childhood. Linkage analysis and search for candidate genes are two complementary strategies aimed at identifying the genes responsible for these disorders.