Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation.
An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the T psi C loop of the tRNA(Lys) gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age-related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.
Shoffner
J M
JM
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322.
Lott
M T
MT
Lezza
A M
AM
Seibel
P
P
Ballinger
S W
SW
Wallace
D C
DC
D000225:Adenine; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000473:pathology; D005260:Female; D006147:Guanine; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D015345:Oligonucleotide Probes; D010375:Pedigree; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics*; D012357:RNA, Transfer, Lys / Q000235:genetics*
D004272:DNA, Mitochondrial; D015345:Oligonucleotide Probes; D012345:RNA, Transfer, Amino Acid-Specific; D012357:RNA, Transfer, Lys; D006147:Guanine; D000225:Adenine