title: Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders.
abstract: FHL1 mutations have been associated with various disorders that include reducing body myopathy (RBM), Emery-Dreifuss-like muscular dystrophy, isolated hypertrophic cardiomyopathy, and some overlapping conditions. We report a detailed histochemical, immunohistochemical, electron microscopic, and immunoelectron microscopic analyses of muscle biopsies from 18 patients carrying mutations in FHL1: 14 RBM patients (Group 1), 3 Emery-Dreifuss muscular dystrophy patients (Group 2), and 1 patient with hypertrophic cardiomyopathy and muscular hypertrophy (Group 2). Group 1 muscle biopsies consistently showed RBs associated with cytoplasmic bodies. The RBs showed prominent FHL1 immunoreactivity whereas desmin, αB-crystallin, and myotilin immunoreactivity surrounded RBs. By electron microscopy, RBs were composed of electron-dense tubulofilamentous material that seemed to spread progressively between the myofibrils and around myonuclei. By immunoelectron microscopy, FHL1 protein was found exclusively inside RBs. Group 2 biopsies showed mild dystrophic abnormalities without RBs; only minor nonspecific myofibrillar abnormalities were observed under electron microscopy. Molecular analysis revealed missense mutations in the second FHL1 LIM domain in Group 1 patients and ins/del or missense mutations within the fourth FHL1 LIM domain in Group 2 patients. Our findings expand the morphologic features of RBM, clearly demonstrate the localization of FHL1 in RBs, and further illustrate major morphologic differences among different FHL1-related myopathies.
authors: Unité de Morphologie Neuromusculaire, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.
authors: Edoardo
authors: E
authors: Malfatti
authors: Montse
authors: M
authors: Olivé
authors: Ana Lía
authors: AL
authors: Taratuto
authors: Pascale
authors: P
authors: Richard
authors: Guy
authors: G
authors: Brochier
authors: Marc
authors: M
authors: Bitoun
authors: Lucie
authors: L
authors: Gueneau
authors: Pascal
authors: P
authors: Laforêt
authors: Tanya
authors: T
authors: Stojkovic
authors: Thierry
authors: T
authors: Maisonobe
authors: Soledad
authors: S
authors: Monges
authors: Fabiana
authors: F
authors: Lubieniecki
authors: Gabriel
authors: G
authors: Vasquez
authors: Nathalie
authors: N
authors: Streichenberger
authors: Emmanuelle
authors: E
authors: Lacène
authors: Maria
authors: M
authors: Saccoliti
authors: Bernard
authors: B
authors: Prudhon
authors: Marilena
authors: M
authors: Alexianu
authors: Dominique
authors: D
authors: Figarella-Branger
authors: Joachim
authors: J
authors: Schessl
authors: Carsten
authors: C
authors: Bonnemann
authors: Bruno
authors: B
authors: Eymard
authors: Michel
authors: M
authors: Fardeau
authors: Gisèle
authors: G
authors: Bonne
authors: Norma Beatriz
authors: NB
authors: Romero
mesh_terms: D000293:Adolescent; D000328:Adult; D000083144:Autosomal Emery-Dreifuss Muscular Dystrophy; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000473:pathology; D002648:Child; D064211:Connectin; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004252:DNA Mutational Analysis; D003893:Desmin / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060588:LIM Domain Proteins / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009135:Muscular Diseases / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D055815:Young Adult; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: D064211:Connectin; D003598:Cytoskeletal Proteins; D003893:Desmin; C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D038203:alpha-Crystallin B Chain
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