MITOCHONDRIAL ENCEPHALOMYOPATHIES - CLINICAL AND MOLECULAR ANALYSIS

The classification of mitochondrial encephalomyopathies relied upon cl inical, biochemical, and histological features until the discovery of mitochondrial DNA defects in 1988. Since then, an outburst of molecula r genetic information has aided our understanding of the pathogenesis and the classification of these heterogeneous disorders. Novel concept s of maternal inheritance, mitochondrial DNA (mtDNA) heteroplasmy, tis sue distribution, and threshold have explained many of the clinical ch aracteristics. The discovery of point mutations, large-scale mtDNA del etions, duplications, and autosomally inherited disorders with multipl e mtDNA deletions have revealed new genetic phenomena. Despite our rap idly expanding understanding of the molecular genetic defects, many qu estions remain to be explored to fill the gap in our knowledge of the relationship between genotype and clinical phenotype.