A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy
- An I Jonckheere1,
- Marije Hogeveen1,
- Leo Nijtmans1,
- Mariel van den Brand1,
- Antoon Janssen1,
- Heleen Diepstra1,
- Frans van den Brandt1,
- Bert van den Heuvel1,
- Frans Hol1,
- Tom Hofste1,
- Livia Kapusta1,
- U Dillmann2,
- M Shamdeen2,
- J Smeitink1,
- J Smeitink1,
- Richard Rodenburg1
- 1Geert Grooteplein 10 PO Box 9101, 6500 HB Nijmegen, Netherlands
- 2Saarland University, Saarbrucken, 66123, Germany
- j.smeitink{at}cukz.umcn.nl
- Published 23 January 2009
Summary
To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder.
Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing.
A homoplasmic nonsense mutation m.8529G→A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient’s fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient’s fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNA
We describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme.
Footnotes
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Competing interests: none.
