Herein we report the clinical and the most relevant molecular genetic findings obtained in a LHON family with a new mitochondrial DNA mutations at np 14498 in the ND 6 gene.
Electron transfer properties of NADH:ubiquinone reductase in the ND13460 and the ND411778 mutations of the Leber hereditary optic neuroretinopathy (LHON).
Biochemical and molecular genetic evidence is presented that in six independent pedigrees the development of Leber hereditary optic neuropathy (LHON) is due to the same primary mutation in the mitochondrial ND1 gene.
Electron transfer properties of NADH:ubiquinone reductase in the ND13460 and the ND411778 mutations of the Leber hereditary optic neuroretinopathy (LHON).
The nucleotide pair (np) 13708 mutation (G to A, ND5 gene) changed an alanine to a threonine and was found in 6/25 (24%) of non-11778 LHON pedigrees and in 5.0% of controls, the np 15257 mutation (G to A, cytochrome b gene) changed an aspartate to an asparagine and was found in 4 of the 13708-positive pedigrees and 0.3% of controls, the np 15812 mutation (G to A, cytochrome b gene) changed a valine to a methionine and was detected in two of the 15257-positive pedigrees and 0.1% of controls and the np 5244 mutation (G to A, ND2 gene) changed a glycine to a serine and was found in one of the 15812-positive patients and none of 2103 controls.
The superimposition of the LHON mutation screening results upon the Caucasian mtDNA phylogeny revealed (1) 35 different LHON haplotypes, (2) that all three common primary mutations have occurred multiple times in Caucasians, (3) that while recurrent mutation is common for the primary mutations, secondary mutations tend to be lineage-specific, (4) that the np 15257 mutation was confined to a single mtDNA lineage but may be etiologically important in some LHON cases since it was found in a LHON pedigree which lacked a common primary mutation; complete sequence analysis of the proband mtDNA revealed only a single other candidate missense mutation (at np 10663 of the ND4L gene) of uncertain pathological significance; and (5) that the np 14484 mutation may be less pathogenic than either the np 3460 or np 11778 mutations, as this mutation most commonly occurred on a single mtDNA lineage and almost always in association with secondary LHON mutations.
A mitochondrial mutation at nt 9101 in the ATP synthase 6 gene associated with deficient oxidative phosphorylation in a family with Leber hereditary optic neuroretinopathy.
The nucleotide pair (np) 13708 mutation (G to A, ND5 gene) changed an alanine to a threonine and was found in 6/25 (24%) of non-11778 LHON pedigrees and in 5.0% of controls, the np 15257 mutation (G to A, cytochrome b gene) changed an aspartate to an asparagine and was found in 4 of the 13708-positive pedigrees and 0.3% of controls, the np 15812 mutation (G to A, cytochrome b gene) changed a valine to a methionine and was detected in two of the 15257-positive pedigrees and 0.1% of controls and the np 5244 mutation (G to A, ND2 gene) changed a glycine to a serine and was found in one of the 15812-positive patients and none of 2103 controls.
New mitochondrial DNA mutations were discovered in the cytochrome c oxidase subunit III gene in 8 independent Leber hereditary optic neuropathy probands.
The nucleotide pair (np) 13708 mutation (G to A, ND5 gene) changed an alanine to a threonine and was found in 6/25 (24%) of non-11778 LHON pedigrees and in 5.0% of controls, the np 15257 mutation (G to A, cytochrome b gene) changed an aspartate to an asparagine and was found in 4 of the 13708-positive pedigrees and 0.3% of controls, the np 15812 mutation (G to A, cytochrome b gene) changed a valine to a methionine and was detected in two of the 15257-positive pedigrees and 0.1% of controls and the np 5244 mutation (G to A, ND2 gene) changed a glycine to a serine and was found in one of the 15812-positive patients and none of 2103 controls.