Journal article

Respiratory chain complex I deficiency caused by mitochondrial DNA mutations

Helen Swalwell, Denise M Kirby, Emma L Blakely, Anna Mitchell, Renato Salemi, Canny Sugiana, Alison G Compton, Elena J Tucker, Xia Ke, Phillipa J Lamont, Douglass M Turnbull, Robert McFarland, Robert W Taylor, David R Thorburn

European Journal of Human Genetics | NATURE PUBLISHING GROUP | Published : 2011


Defects of the mitochondrial respiratory chain are associated with a diverse spectrum of clinical phenotypes, and may be caused by mutations in either the nuclear or the mitochondrial genome (mitochondrial DNA (mtDNA)). Isolated complex I deficiency is the most common enzyme defect in mitochondrial disorders, particularly in children in whom family history is often consistent with sporadic or autosomal recessive inheritance, implicating a nuclear genetic cause. In contrast, although a number of recurrent, pathogenic mtDNA mutations have been described, historically, these have been perceived as rare causes of paediatric complex I deficiency. We reviewed the clinical and genetic findings in a..

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Awarded by Medical Research Council

Awarded by National Institute for Health Research

Funding Acknowledgements

We thank the large number of physicians who referred patients for investigative studies, Dr Henrik Dahl for advice and Drs Vamsi Mootha and Sarah Calvo for identification of three of the mtDNA mutations described herein, as part of a High Throughput sequencing study of complex I deficiency. We also thank Drs Lisa Worgan, Edwin Kirk, Peter Taylor and Michael Buckley for the dHPLC analyses that identified subunit mutations in five patients. This work was supported by grants and a Principal Research Fellowship from the Australian National Health and Medical Research Council (DRT), the Muscular Dystrophy Association, USA (DRT), the Medical Research Council, UK (RM) and the Wellcome Trust, UK (DMT and RWT). Diagnostic studies in the Newcastle laboratory are supported by the UK National Commissioning Group 'Rare Mitochondrial Disorders of Adults and Children' service ( This study was performed under the ethical guidelines issued by each of our Institutions for clinical studies.