Segregation and manifestations of the mtDNA tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome

Journal Article · Tue Dec 01 04:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:6717621

Larsson, N G; Tulinius, M H; Holme, E; Oldfors, A; Andersen, O; Wahlstroem, J ^[1]; Aasly, J ^[2]

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1. Univ. of Gothenburg (Sweden)
2. Univ. of Trondheim (Norway)

The authors have studied the segregation and manifestations of the tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA[sup Lys] mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, and mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrone had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that >92% of mtDNA with the tRNA[sup Lys] mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA[sup Lys] mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. 30 refs., 3 figs., 5 tabs.

• OSTI ID: 6717621
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 51:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CYTOCHROME OXIDASE
DISEASES
DISTRIBUTION
ENZYME ACTIVITY
ENZYMES
EPILEPSY
FIBERS
GENES
HAEM DEHYDROGENASES
LEVELS
LYSINE
METABOLIC DISEASES
MITOCHONDRIA
MUSCLES
MUTATIONS
MYOBLASTS
NERVOUS SYSTEM DISEASES
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATIENTS
PHENOTYPE
PROTEINS
RESIDUES
RNA
SIZE
TRANSFER RNA