Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene

Authors

  • Cristina Ugalde PhD,

    Corresponding author
    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
    • Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
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  • Ralf H. Triepels PhD,

    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
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  • Marieke J.H. Coenen MSc,

    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
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  • Lambert P. Van Den Heuvel PhD,

    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
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  • Roel Smeets,

    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
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  • Johanna Uusimaa MD, PhD,

    1. Department of Neurology and Biocenter, University of Oulu, Oulu, Finland
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  • Paz Briones PhD,

    1. Institut de Bioquímica Clínica, Corporació Sanitaria Clínic y CSIC, Barcelona, Spain
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  • Jaume Campistol MD, PhD,

    1. Servicio Neurologia, Unidad Intregrada Hospital Sant Joan de Déu-Clínic, Universidad de Barcelona, Spain
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  • Kari Majamaa MD, PhD,

    1. Department of Neurology and Biocenter, University of Oulu, Oulu, Finland
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  • Jan A.M. Smeitink MD, PhD,

    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
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  • Leo G.J. Nijtmans PhD

    1. Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
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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.

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