The role of complex I genes in MELAS: a novel heteroplasmic mutation 3380G>A in ND1 of mtDNA.
While Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is typically associated with mutations in the mitochondrial tRNA(Leu) gene, mutations in complex I subunit genes of the mtDNA have emerged as a second significant cause. Here we report a novel mutation in the mitochondrial complex I subunit gene ND1 in a patient with late-onset MELAS. The 3380G>A mutation shows very good evidence of pathogenicity as it is heteroplasmic, undetectable in controls, alters a highly conserved amino acid, and is more abundant in ragged-red than in normal muscle fibers. These findings support the significant role of complex I mutations in MELAS.
Horváth
Rita
R
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University, Munich, Ziemssenstr. 1, 80336 Munich, Germany.
Reilmann
Ralf
R
Holinski-Feder
Elke
E
Ringelstein
E Bernd
EB
Klopstock
Thomas
T
D000704:Analysis of Variance; D000818:Animals; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000502:physiology*; D005192:Family Health; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D018709:Statistics, Nonparametric
D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human; D042967:Electron Transport Complex I