[Mitochondrial encephalomyopathies: 3243 mutation as a central matter].

Molecular diagnosis for mitochondrial diseases offers a powerful means to clarify that mitochondrial DNA (mtDNA) defects have different characteristics from those of nuclear DNA. Regarding the relationship between genotype and phenotype, there is a dual heterogeneity. It means that one mutation, for example, a 3243 mutation, has several clinical phenotypes, including MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), myopathy only, diabetes and/or deafness and even CPEO (chronic progressive external ophthalmoplegia). Conversely, one phenotype, for instance, MELAS has several genetypes; 3243, 3271, and 3291 mutations. The second unique event in mitochondrial DNA mutation is heterogenous distribution of mutant mtDNA in a mitochondrion or a cell that is called heteroplasmy. The extend of heteroplasmy seems different from tissue to tissue providing clues to explain the variability of tissue impairment and heterogenous clinical symptoms. The above evidence suggests that we should take care in selecting tissues to be tested. The third problem remained is on maternal inheritance. It makes the genetic counselling on mitochondrial diseases at clinics difficult and laborious. In conclusion, mtDNA analysis must be used as a last resort to get final diagnosis.