Premium
The influence of nuclear background on the biochemical expression of 3460 Leber's hereditary optic neuropathy
Author(s) -
Cock H. R.,
Tabrizi S. J.,
Cooper J. M.,
Schapira A. H. V.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440208
Subject(s) - leber's hereditary optic neuropathy , heteroplasmy , mitochondrial dna , optic neuropathy , mutation , genetics , biology , microbiology and biotechnology , pathogenesis , mutant , nuclear dna , mitochondrial disease , gene , optic nerve , neuroscience , immunology
Abstract The role of mitochondrial DNA (mtDNA) mutations in the pathogenesis of Leber's hereditary optic neuropathy (LHON) has yet to be characterized. Several clinical feature of the disease imply that nuclear genes might also be involved in its expressions. We have confirmed the presence of a severe NADH:coenzyme Q 1 reductase (complex I) defect in association with the A3460G mtDNA LHON mutation in cultured fibroblasts compared with age‐matched controls. This defect was not seen in clonal fibroblasts with 0% mutant mtDNA developed from a heteroplasmic A3460G LHON subject, confirming the association between the A3460G mutation and the complex I defect. Cybrids prepared from the fusion of enucleated fibroblasts homplasmic for the A3460G mutation with 206 (osteosarcoma) cells lacking mtDNA (ρ o ) also had a severe deficiency of complex I activity. However, in A3460G LHON fusion cybrids containing a different nuclear background, A549 ρ O (lung derived), this biochemical defect was not apparent in all the clones studied. These results suggest that the nuclear environment can influence the expression of the biochemical defect in LHON patients with the A3460G mutation.