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

Cristina Ugalde; Ralf H Triepels; Marieke J H Coenen; Lambert P van den Heuvel; Roel Smeets; Johanna Uusimaa; Paz Briones; Jaume Campistol; Kari Majamaa; Jan A M Smeitink; Leo G J Nijtmans

doi:10.1002/ana.10734

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

Ann Neurol. 2003 Nov;54(5):665-9. doi: 10.1002/ana.10734.

Authors

Cristina Ugalde¹, Ralf H Triepels, Marieke J H Coenen, Lambert P van den Heuvel, Roel Smeets, Johanna Uusimaa, Paz Briones, Jaume Campistol, Kari Majamaa, Jan A M Smeitink, Leo G J Nijtmans

Affiliation

¹ 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

PMID: 14595656
DOI: 10.1002/ana.10734

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Cells, Cultured
DNA Mutational Analysis
DNA, Mitochondrial / genetics*
Electron Transport Complex I / genetics*
Electron Transport Complex I / metabolism
Fibroblasts / physiology
Humans
Infant
Leigh Disease / genetics*
Male
Mutation, Missense
Polymerase Chain Reaction

Substances

DNA, Mitochondrial
Electron Transport Complex I