Novel STAC3 Mutations in the First Non-Amerindian Patient with Native American Myopathy.

December 01, 2017

Grzybowski M1, Schänzer A2, Pepler A3, Heller C3,Neubauer BA1,Hahn A1.

Abstract

Native American myopathy (NAM) is an autosomal recessive congenital myopathy, up till now exclusively described in Lumbee Indians who harbor one single homozygous mutation (c.1046G>C, pW284S) in the STAC3 gene, encoding a protein important for proper excitation-contraction coupling in muscle. Here, we report the first non-Amerindian patient of Turkish ancestry, being compound heterozygous for the mutations c.862A>T (p.K288*) and c.432+4A>T (aberrant splicing with skipping of exon 4). Symptoms in NAM include congenital muscle weakness and contractures, progressive scoliosis, early ventilatory failure, a peculiar facial gestalt with mild ptosis and downturned corners of the mouth, short stature, and marked susceptibility to malignant hyperthermia. This case shows that NAM should also be considered in non-Indian patients with congenital myopathy, and suggests that STAC3 mutations should be taken into account as a potential cause of malignant hyperthermia.

  1. Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
  2. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
  3. Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
  4. Institut für Humangenetik, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
  5. MVZ Labor Krone, Filialpraxis für Humangenetik, Bielefeld, Germany.
  6. Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
  7. Cologne Center for Genomics (CCG), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
  8. Core Facility Genomics, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany.
  9. Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
  10. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  11. Institut für Humangenetik, Westfälische Wilhelms-Universität Münster, Münster, Germany.
  12. CeGaT GmbH, Center for Genomics and Transcriptomics, Tübingen, Germany.
  13. Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology and Metabolism, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, Netherlands.
  14. Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany.
  15. Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
  16. Institute of Human Genetics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
  17. Research Group Structure and Function of Molecular Machines, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
  18. Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
  19. Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable cells” (MBExC), University of Göttingen, Göttingen, Germany.
  20. DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany.