ADVANCES IN THE GENETIC MECHANISMS OF MITOCHONDRIAL DISEASE

During the past 16 years since the delineation of the human mitochondr ial genome, substantial advances have been made in identifying pathoge nic mutations causing mitochondrial disorders. However, just as we hav e come to accept the unexpected in the nontraditional aspects of Mende lian inheritance with the discovery of trinucleotide expansions, impri nting and uniparental disomy, unusual characteristics of mitochondrial inheritance also have been found that defy existing laws. For example , we now know that the nuclear genetic background of an individual mig ht influence the expression and tissue specificity of mitochondrial mu tations. Pathogenic mitochondrial DNA mutations contribute to the gene ration of new mutations by compromising mitochondrial function and inc reasing free radical production. Evidence for recombination raises new questions about repair mechanisms of mitochondrial DNA. It appears th at the more we learn about the bases of mitochondrial disease, the mor e complex diagnosis, treatment, and genetic counseling become. (C) Rap id Science Publishers.