GENE DOSAGE EFFECT IN ONE FAMILY WITH MYOCLONIC EPILEPSY AND RAGGED-RED FIBERS (MERRF)

Objectives - We analyzed the percentage of mitochondrial DNA (mtDNA) h eteroplasmy in blood samples of 13 individuals belonging to a three fa mily generation of myoclonic epilepsy with ragged-red fibers (MERRF) a nd compared the 5 affected patients and the 8 unaffected relatives. Ma terial and methods - DNA was extracted from blood and muscle of the pr oband and from blood of 12 maternal relatives. A PCR restriction analy sis method was used to detect the mutation. Results - The proband had the complete MERRF phenotype. The phenotype in three other individuals in the maternal lineage was consistent with the MERRF syndrome. The r emaining were asymptomatic. The np 8344 mutation was observed in muscl e and blood of the proband, and in blood from every one of 12 maternal relatives, ranging from 44% to 83% of mutated genomes. Symptomatic in dividuals had higher levels (P<0.001) of mutated mtDNA than asymptomat ic maternal relatives. However, high proportions of mutant genomes (up to 63%) were found in asymptomatic relatives. Conclusions - Although there seems to be a gene dosage effect in MERRF, we found no absolute relationship between the relative proportion of mutant genomes in bloo d and clinical severity. Factors other than gene dosage in blood may a ccount for the differences in clinical phenotype.