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CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies.
Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert D S; Hilton-Jones, David; Schapira, Anthony H; Turner, Chris; Parton, Matt; Desikan, Mahalekshmi; Barresi, Rita; Marsh, Julie; Manzur, Adnan Y; Childs, Anne-Marie; Feng, Lucy; Murphy, Elaine; Lamont, Phillipa J; Ravenscroft, Gianina; Wallefeld, William; Davis, Mark R; Laing, Nigel G; Holton, Janice L; Fialho, Doreen; Bushby, Kate; Hanna, Michael G; Phadke, Rahul; Jungbluth, Heinz; Houlden, Henry; Quinlivan, Ros.
Afiliación
  • Scalco RS; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; CAPES Foundation, Ministry of Education of Brazil, Brasilia DF, Brazil. Electronic address:
  • Gardiner AR; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Pitceathly RD; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neur
  • Hilton-Jones D; Department of Clinical Neurology, West Wing, John Radcliffe Hospital, Oxford, UK.
  • Schapira AH; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Turner C; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Parton M; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Desikan M; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Barresi R; NHS England HSS for Rare Neuromuscular Diseases, Muscle Immunoanalysis Unit, Dental Hospital Richardson Road, Newcastle upon Tyne, UK; The John Walton Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyn
  • Marsh J; NHS England HSS for Rare Neuromuscular Diseases, Muscle Immunoanalysis Unit, Dental Hospital Richardson Road, Newcastle upon Tyne, UK.
  • Manzur AY; Dubowitz Neuromuscular Centre, UCL Institute of Child Health, Great Ormond Street Hospital, London, UK.
  • Childs AM; Leeds Teaching Hospitals, Leeds, UK.
  • Feng L; Dubowitz Neuromuscular Centre, UCL Institute of Child Health, Great Ormond Street Hospital, London, UK.
  • Murphy E; Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Lamont PJ; Neurogenetic Unit, Dept of Neurology, Royal Perth Hospital, Australia.
  • Ravenscroft G; Harry Perkins Institute of Medical Research and the Centre for Medical Research, University of Western Australia, Nedlands, Australia.
  • Wallefeld W; Department of Diagnostic Genomics, Pathwest, QEII Medical Centre, Nedlands, Australia.
  • Davis MR; Department of Diagnostic Genomics, Pathwest, QEII Medical Centre, Nedlands, Australia.
  • Laing NG; Harry Perkins Institute of Medical Research and the Centre for Medical Research, University of Western Australia, Nedlands, Australia; Department of Diagnostic Genomics, Pathwest, QEII Medical Centre, Nedlands, Australia.
  • Holton JL; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Fialho D; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Bushby K; The John Walton Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Hanna MG; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Phadke R; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Dubowitz Neuromuscular Centre, UCL Institute of Child Health, Great Ormond Street Hospital,
  • Jungbluth H; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Department of Paediatric Neurology, Evelina Children's Hospital, Guy's & St Thomas NHS Foundation Trust, London, UK; Randall Division for Cell and Molecular Biophysics,
  • Houlden H; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
  • Quinlivan R; MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Dubowitz Neuromuscular Centre, UCL Institute of Child Health, Great Ormond Street Hospital,
Neuromuscul Disord ; 26(8): 504-10, 2016 08.
Article en En | MEDLINE | ID: mdl-27312022
Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiólisis / Tolerancia al Ejercicio / Caveolina 3 / Mialgia Límite: Adolescent / Adult / Aged80 / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Neuromuscul Disord Asunto de la revista: NEUROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiólisis / Tolerancia al Ejercicio / Caveolina 3 / Mialgia Límite: Adolescent / Adult / Aged80 / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Neuromuscul Disord Asunto de la revista: NEUROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido