A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and ragged-red fibers (MERRF).
Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A--G transition at mtDNA nt 8344, within a conserved region of the tRNA(Lys) gene. Although the 8344 mutation is highly prevalent in patients with MERRF, it is not observed in 10%-20% of the cases, suggesting genetic heterogeneity. We have sequenced the tRNA(Lys) gene of five MERRF patients lacking the common 8344 mutation. One of these showed a novel T-->C transition at nucleotide position 8356, disrupting a highly conserved base pair in the T psi C stem. The mutant mtDNA population was essentially homoplasmic in muscle but was heteroplasmic in blood (47%). Neither 20 patients with other mitochondrial diseases nor 25 controls carried this mutation. These findings suggest that tRNA(Lys) alterations may play a specific role in the pathogenesis of MERRF syndrome.
Silvestri
G
G
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Moraes
C T
CT
Shanske
S
S
Oh
S J
SJ
DiMauro
S
S
D000328:Adult; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D012357:RNA, Transfer, Lys / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D004272:DNA, Mitochondrial; D012357:RNA, Transfer, Lys