A novel heteroplasmic point mutation in the mitochondrial tRNA(Lys) gene in a sporadic case of mitochondrial encephalomyopathy: de novo mutation and no transmission to the offspring.
We have identified a new mutation in the tRNA(Lys) gene of mtDNA, in a 49-year-old patient with mitochondrial encephalomyopathy. The mutation is a heteroplasmic G-->A transition at position 8328, which affects the anticodon stem loop at a conserved site. The mutation was neither found in 100 controls nor in the maternal relatives of the patient. The level of mutated mtDNA was 57% in muscle, 13% in fibroblasts, and 10% in lymphocytes. Histochemistry of muscle tissue revealed cytochrome c oxidase-deficient fibers with abnormal accumulation of mitochondria. Biochemistry of muscle mitochondria showed slight cytochrome c oxidase deficiency. The mean ratio of mutant mtDNA to normal mtDNA in cytochrome c oxidase-positive muscle fibers was 59%, whereas a mean ratio of 95% was found in cytochrome c oxidase-negative fibers. The difference between cytochrome c oxidase-positive and cytochrome c oxidase-negative fibers was highly significant (P < 0.001). The mutation was not found in muscle or lymphocytes of the mother and daughter of the proband. This is the first report of a de novo point mutation in the tRNA(Lys) gene in an individual expressing disease and the first report of lack of transmission of the mutation to the offspring of a patient expressing a mitochondrial encephalomyopathy caused by a point mutation in mtDNA.
Houshmand
M
M
Department of Clinical Chemistry, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden.
Lindberg
C
C
Moslemi
A R
AR
Oldfors
A
A
Holme
E
E
D001483:Base Sequence; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009132:Muscles / Q000033:anatomy & histology / Q000648:ultrastructure; D010375:Pedigree; D017354:Point Mutation; D012357:RNA, Transfer, Lys / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D004272:DNA, Mitochondrial; D012357:RNA, Transfer, Lys; D003576:Electron Transport Complex IV