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Two Novel Mutations in the SLC25A4 Gene in a Patient with Mitochondrial Myopathy

  • I. M. L. W. Körver-Keularts
  • M. de Visser
  • H. D. Bakker
  • R. J. A. Wanders
  • F. Vansenne
  • H. R. Scholte
  • L. Dorland
  • G. A. F. Nicolaes
  • L. M. J. Spaapen
  • H. J. M. Smeets
  • A. T. M. Hendrickx
  • B. J. C. van den Bosch
Case Report
Part of the JIMD Reports book series (JIMD, volume 22)

Abstract

In a 28-year-old male with a mild mitochondrial myopathy manifesting as exercise intolerance and early signs of cardiomyopathy without muscle weakness or ophthalmoplegia, we identified two novel mutations in the SLC25A4 gene: c.707G>C in exon 3 (p.(R236P)) and c.116_137del in exon 2 (p.(Q39Lfs*14)). Serum lactate levels at rest were elevated (12.7 mM). Both the patient’s father and brother were heterozygous carriers of the c.707G>C mutation and were asymptomatic. The second mutation causes a 22 bp deletion leading to a frame shift likely giving rise to a premature stop codon and nonsense-mediated decay (NMD). The segregation of the mutations could not be tested directly as the mother had died before. However, indirect evidence from NMD experiments showed that the two mutations were situated on two different alleles in the patient. This case is unique compared to other previously reported patients with either progressive external ophthalmoplegia (PEO) or clear hypertrophic cardiomyopathy with exercise intolerance and/or muscle weakness carrying recessive mutations leading to a complete absence of the SLC25A4 protein. Most likely in our patient, although severely reduced, SLC25A4 is still partially present and functional.

Keywords

Hypertrophic cardiomyopathy Mitochondrial myopathy Novel mutations SLC25A4 

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • I. M. L. W. Körver-Keularts
    • 1
  • M. de Visser
    • 2
  • H. D. Bakker
    • 3
  • R. J. A. Wanders
    • 4
  • F. Vansenne
    • 5
  • H. R. Scholte
    • 6
  • L. Dorland
    • 1
  • G. A. F. Nicolaes
    • 7
  • L. M. J. Spaapen
    • 1
  • H. J. M. Smeets
    • 8
  • A. T. M. Hendrickx
    • 8
  • B. J. C. van den Bosch
    • 8
  1. 1.Department of Clinical Genetics, Lab of Biochemical GeneticsMaastricht University Medical CenterMaastrichtThe Netherlands
  2. 2.Department of Neurology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of Paediatrics, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  4. 4.Laboratory Genetic Metabolic Diseases, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  5. 5.Department of Clinical Genetics, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  6. 6.Department of NeuroscienceErasmus Medical CenterRotterdamThe Netherlands
  7. 7.Department of Biochemistry, Cardiovascular Research Institute MaastrichtMaastricht UniversityMaastrichtThe Netherlands
  8. 8.Department of Clinical Genetics, Unit Clinical GenomicsMaastricht University Medical CenterMaastrichtThe Netherlands

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