Gene dosage effect in one family with myoclonic epilepsy and ragged-red fibers (MERRF).
OBJECTIVE
We analyzed the percentage of mitochondrial DNA (mtDNA) heteroplasmy in blood samples of 13 individuals belonging to a three family generation of myoclonic epilepsy with ragged-red fibers (MERRF) and compared the 5 affected patients and the 8 unaffected relatives.


METHODS
DNA was extracted from blood and muscle of the proband and from blood of 12 maternal relatives. A PCR restriction analysis 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 remaining were asymptomatic. The np 8344 mutation was observed in muscle and blood of the proband, and in blood from every one of 12 maternal relatives, ranging from 44% to 83% of mutated genomes. Symptomatic individuals had higher levels (P < 0.001) of mutated mtDNA than asymptomatic 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 blood and clinical severity. Factors other than gene dosage in blood may account for the differences in clinical phenotype.
Arpa
J
J
Department of Neurology, Hospital La Paz, Madrid, Spain.
Campos
Y
Y
Gutiérrez-Molina
M
M
Martin-Casanueva
M A
MA
Cruz-Martínez
A
A
Pérez-Conde
M C
MC
López-Pajares
R
R
Morales
M C
MC
Tatay
J
J
Lacasa
T
T
Barreiro
P
P
Arenas
J
J
D000328:Adult; D017668:Age of Onset; D003402:Creatine Kinase / Q000097:blood; D004272:DNA, Mitochondrial / Q000032:analysis / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D014644:Genetic Variation / Q000235:genetics* / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D017243:MERRF Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000502:physiology*; D012720:Severity of Illness Index
D004272:DNA, Mitochondrial; D019344:Lactic Acid; D003402:Creatine Kinase