Novel FHL1 mutation in a family with reducing body myopathy

Authors

  • Tobias Schreckenbach,

    1. Institute of Neuropathology, University Hospital Aachen, Aachen, Germany
    2. Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany
    3. Jülich Aachen Research Alliance (JARA) Brain, Jülich, Germany
    Search for more papers by this author
  • Wolfram Henn MD,

    1. Institute for Human Genetics, Saarland University, Homburg, Germany
    Search for more papers by this author
  • Wolfram Kress MD, PhD,

    1. Institute for Human Genetics, Würzburg, Germany
    Search for more papers by this author
  • Andreas Roos PhD,

    1. Institute of Neuropathology, University Hospital Aachen, Aachen, Germany
    2. Jülich Aachen Research Alliance (JARA) Brain, Jülich, Germany
    Search for more papers by this author
  • Matthias Maschke MD,

    1. Department of Neurology, Brüderkrankenhaus, Trier, Germany
    Search for more papers by this author
  • Wolfgang Feiden MD,

    1. Medizinisches Versorgungszentrum für Histologie, Zytologie und Molekulare Diagnostik, Trier, Germany
    2. Institute of Neuropathology, University Hospital Homburg Saar, Homburg, Germany
    Search for more papers by this author
  • Ulrich Dillmann MD,

    1. Department of Neurology, University Hospital Homburg Saar, Homburg, Germany
    Search for more papers by this author
  • Jörg B. Schulz MD,

    1. Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany
    2. Jülich Aachen Research Alliance (JARA) Brain, Jülich, Germany
    Search for more papers by this author
  • Joachim Weis MD,

    1. Institute of Neuropathology, University Hospital Aachen, Aachen, Germany
    2. Jülich Aachen Research Alliance (JARA) Brain, Jülich, Germany
    Search for more papers by this author
  • Kristl G. Claeys MD, PhD

    Corresponding author
    1. Institute of Neuropathology, University Hospital Aachen, Aachen, Germany
    2. Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany
    3. Jülich Aachen Research Alliance (JARA) Brain, Jülich, Germany
    • Klinik für Neurologie and Institut für Neuropathologie, Universitätsklinikum der RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany

    Search for more papers by this author

Abstract

Introduction: Reducing body myopathy is a rare X-linked myopathy. It is characterized by intracytoplasmic inclusions that stain with menadione–nitroblue tetrazolium. It is caused by mutations in the FHL1 gene, which encodes the four-and-a-half LIM domain 1 protein (FHL1). Methods: We performed a clinical, muscle MRI, and histopathological characterization and immunoblot and genetic analysis of the FHL1 protein in a family with 4 individuals affected by reducing body myopathy. Results: We identified a novel missense mutation in FHL1 (c.449G>C; p.C150S). The patients presented with asymmetric proximal weakness and scoliosis. Both of the boys had a more severe course with earlier onset, contractures, and death due to heart failure at 14 and 18 years of age, respectively. MRI revealed fatty infiltration of posteromedial thigh and paraspinal muscles. Histopathological findings showed FHL1-immunoreactive inclusions. Immunoblot analysis revealed a 50% reduction of FHL1 protein. Conclusion: In this study we highlighted diagnostic clues in this myopathy and compared our data with the literature. Muscle Nerve, 2013

Ancillary