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Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene
Authors:Edoardo Malfatti  Ursula Schaeffer  Françoise Chapon  Yage Yang  Bruno Eymard  Ran Xu  Jocelyn Laporte  Norma B. Romero
Affiliation:1. Unité de Morphologie Neuromusculaire, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France;2. Department of Neurological, Neurosurgical, and Behavioral Sciences, University of Siena, Siena, Italy;3. Inserm, U974, Paris F-75013, France;4. Université Pierre et Marie Curie-Paris 6, UM 76, CNRS, UMR 7215, Institut de Myologie, IFR14, Paris F-75013, France;5. Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, GHU La Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France;6. Department of Translational Medicine and Neurogenetics, IGBMC, Illkirch, France;7. Inserm, U964, Illkirch, France;8. CNRS, UMR7104, Illkirch, France;9. Université de Strasbourg, Illkirch, France;10. Collège de France, Chaire de Génétique Humaine, Illkirch, France;11. CHU de Caen, Centre de Compétences des Pathologies Neuro-musculaires, Côte de Nacre, INSERM U 1075 COMETE, 14033 CAEN Cedex, France;12. BGI-Shenzhen, Shenzhen 518083, China;1. Department of Paediatric Neurology – Neuromuscular Service, Evelina Children’s Hospital, St Thomas’ Hospital, London, UK;2. Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, London, UK;3. Clinical Neuroscience Division, King’s College, London, UK;4. Department of Medical Genetics, Haartman Institute, University of Helsinki, Biomedicum Helsinki, Finland;5. The Folkhälsan Department of Medical Genetics, Helsinki, Finland;6. Department of Translational Medecine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch F-67404, France;7. Inserm, U964, Illkirch F-67404, France;8. CNRS, UMR7104, Illkirch F-67404, France;9. Université de Strasbourg, Strasbourg F-67404, France;10. Collège de France, Illkirch F-67404, France;1. MRC Centre for Neuromuscular Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;2. Oxford MDC Muscle and Nerve Centre, West Wing, John Radcliffe Hospital, Oxford, UK;3. Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK;1. Groupe de recherche interdisciplinaire en maladies neuromusculaires (GRIMN), Centre de santé et de services sociaux de Jonquière, Québec, Canada;2. Faculty of Medicine and Health Sciences, Université de Sherbrooke, Québec, Canada;3. Department of Neurology, University of Milan, IRCCS Policlinico San Donato, Italy;4. Human Genetics Unit, Centre hospitalier de l’Université Laval, Québec, Canada;5. ÉCOBES, Cégep de Jonquière, Québec, Canada;6. Centre hospitalier universitaire de Chicoutimi, Chicoutimi, Québec, Canada;7. Department of Health Sciences, Université du Québec à Chicoutimi, Québec, Canada;8. Faculty of Medicine, Université Laval, Québec, Canada;9. Canadian Forces Health Services HQ, Directorate of Medical Policy, Québec, Canada;1. CHU Saint-Étienne, Hôpital Bellevue, Department of Paediatric Physical Medicine and Rehabilitation, Rhône-Alpes Reference Centre for Neuromuscular Diseases, Saint-Étienne F-42055, France;2. CHU Saint-Étienne, Hôpital Bellevue, Department of Myology, Rhône-Alpes Reference Centre for Neuromuscular Diseases, Saint-Étienne F-42055, France;3. Exercise Physiology Laboratory, Univ Saint-Étienne, EA 4338, Saint-Étienne F-42023, France;4. CHU Saint-Étienne, Hôpital nord, Department of Neurology, Rhône-Alpes Reference Centre for Neuromuscular Diseases, Saint-Étienne F-42055, France;5. AP-HP, Hôpital de la Pitié-Salpêtrière, Paris-Est Reference Centre for Neuromuscular Diseases, Paris F-75651, France;6. AP-HP, Hôpital Antoine Béclère, Laboratory of Molecular Genetics and Metabolic Diseases, Clamart F-92141, France;1. University of Florida College of Medicine, Gainesville, FL, USA;2. Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC, USA
Abstract:The slow α-tropomyosin gene (TPM3) has been associated with three distinct histological entities: nemaline myopathy (NM, NEM1), congenital fibre-type disproportion (CFTD), and cap disease (CD). Here we describe a patient presenting an early-onset congenital myopathy associated with a combination of well separated cap structures and nemaline bodies in his muscle biopsy. Exome sequencing analysis allowed us to identify a de novo missense mutation in the TPM3 gene. Our study confirms the extreme variability of morphological findings in TPM3-related myopathies, and proves that cap and nemaline bodies are two sides of the same ‘coin’.
Keywords:Congenital structural myopathies  Nemaline myopathies  Cap disease  Exome sequencing
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