Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene.
We describe a novel mutation in the ND6 gene (T14487C) in a patient with Leigh syndrome. Biochemical analyses indicated a low complex I activity in the patient's fibroblasts but normal values in muscle and liver. Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels. Additionally, we demonstrate an altered mobility and a decrease in the levels of fully assembled complex I in the patient's fibroblasts and cybrids, suggesting that the mutation has a profound effect on complex I assembly and/or stability.
Ugalde
Cristina
C
Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. c.ugalde@cukz.umcn.nl
Triepels
Ralf H
RH
Coenen
Marieke J H
MJ
van den Heuvel
Lambert P
LP
Smeets
Roel
R
Uusimaa
Johanna
J
Briones
Paz
P
Campistol
Jaume
J
Majamaa
Kari
K
Smeitink
Jan A M
JA
Nijtmans
Leo G J
LG
D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I