Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene.
,
Ralf H. Triepels,
Marieke J. H. Coenen ,
Lambert P. Van Den Heuvel,
L. P. W. J. van den Heuvel,
Roel Smeets,
Johanna Uusimaa,
Paz Briones,
Jaume Campistol,
Kari Majamaa,
Jan A. M. Smeitink,
Leo G. J. Nijtmans
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Abstract
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.