title: Novel FHL1 mutation in a family with reducing body myopathy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  In this study we highlighted diagnostic clues in this myopathy and compared our data with the literature.
authors.affiliation: Institute of Neuropathology, University Hospital Aachen, Aachen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schreckenbach
authors.forename: Wolfram
authors.initials: W
authors.lastname: Henn
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kress
authors.forename: Andreas
authors.initials: A
authors.lastname: Roos
authors.forename: Matthias
authors.initials: M
authors.lastname: Maschke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Feiden
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dillmann
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
mesh_terms: D000293:Adolescent; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins