Single muscle fiber analysis of myoclonus epilepsy with ragged-red fibers.
We examined two muscle biopsy specimens from a proband and her mother with myoclonus epilepsy with ragged-red fibers (MERRF), both obtained at an interval of about 10 years, using histochemistry, in situ hybridization, and single-fiber polymerase chain reaction. Total (wild-type and mutant) mitochondrial DNAs (mtDNAs) were greatly increased in ragged-red fibers (RRF) over non-RRF in all muscle specimens analyzed. The proportion of mutant mtDNA was also significantly higher in RRF than in non-RRF. By comparing the first and second muscle biopsied specimens in each patient, we found that while the proportion of RRF, cytochrome coxidase deficient fibers, and mutant DNA in muscle changed over a 10-year period, the proportion of wild-type and mutant mtDNAs in RRF and in non-RRF was similar between the two specimens. These results suggest that the ratio of wild-type to mutant mtDNAs in RRF and non-RRF in MERRF is at a steady state level in each muscle fiber, without replicative advantage of mutant mtDNA.
Mita
S
S
Department of Neurology, Kumamoto University School of Medicine, Japan.
Tokunaga
M
M
Uyama
E
E
Kumamoto
T
T
Uekawa
K
K
Uchino
M
M
D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D017403:In Situ Hybridization; D017243:MERRF Syndrome / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009154:Mutation; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial