Leukocyte
mitochondrial DNA (
mtDNA) from 17 Finnish families with Leber's
hereditary optic neuroretinopathy and 70 maternally unrelated controls as well as skeletal muscle
mtDNA from four of the Leber families and three controls was analyzed with 30 restriction
enzymes. By this means, over 10% of the
nucleotides of
mtDNA were screened. No major deletion or insertion was found in any of the mtDNAs studied. The restriction fragment patterns of
mtDNA showed no evidence of
mtDNA heteroplasmy (mixture of different
mtDNA types) in either blood or muscle cells. In all, 24
mtDNA types were observed in the material. In the maternal lines of Leber families, 11
mtDNA types were found, indicating no recent common maternal ancestor for the Finnish Leber families. In spite of several previously unknown polymorphisms, no mutation of
mtDNA could be found exclusively in families with
Leber's disease. However, a couple of mutations leading to
amino acid replacements of mitochondrially encoded
proteins were observed in certain Leber families only. These mutations have occurred in genes coding for subunits of
NADH dehydrogenase, suggesting that a defect of the respiratory chain complex I may cause
Leber's disease.