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.
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University College of Physicians and Surgeons, New York, NY 10032.
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G
Silvestri
C T
CT
Moraes
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Shanske
S J
SJ
Oh
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DiMauro
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