Novel TPM3 mutation in a family with cap myopathy and review of the literature |
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| Affiliation: | 1. Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany;2. Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany;3. Institut de Myologie, Université Pierre et Marie Curie Paris, UM76, INSERM U 974, CNRS UMR 7215, Paris, France;4. Medizinisch Genetisches Zentrum München, München, Germany;5. Institute of Neuropathology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;6. JARA Translational Brain Medicine, Germany;7. Department of Radiology, University Hospital RWTH Aachen, Aachen, Germany;1. Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;2. Hematology, Oncology & Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Medical Genetics, Szentágothai Research Center, University of Pécs, Pécs, Hungary;2. Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany;3. Institute for Genetics, University of Cologne, 50674 Cologne, Germany;4. Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany;5. Neurology Clinic, University of Pécs, Pécs, Hungary;6. deCODE Genetics, Reykjavik, Iceland;1. Department of Neuropathology, Charité – Universitätsmedizin Berlin, Germany;2. Department of Gastroenterology, Infectiology and Rheumatology, Campus, Benjamin Franklin, Charité – Universitätsmedizin Berlin, Germany;1. Neuromuscular Research Unit, Section 3342, Rigshospitalet, University of Copenhagen, Denmark;2. Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark;3. Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Denmark;4. Department of Neurology, Aarhus Hospital, University of Aarhus, Denmark;1. Service de Pédiatrie, Centre de Référence Maladies Neuromusculaires (GNMH), AP-HP, Hôpital Raymond Poincaré, Garches, France;2. Université Versailles UVSQ, France;3. INSERM, UMRS_974, Paris, France;4. S2A Santé, Ivry-sur-Seine, France;5. Service de Pneumologie Pédiatrique, AP-HP, Hôpital Armand Trousseau, Paris, France;6. Clinique Pediatrique, Institut G. Gaslini, Gênes, Italy;7. ADEP ASSISTANCE, Suresnes, France;8. UF Cardiogénétique et Myogénétique, Service de Biochimie Métabolique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France;9. Service de Radiologie, Pole Neuromoteur, AP-HP, Hôpital Raymond Poincaré, Garches, France;10. UPMC Univ., Um76, Paris, 06, France;11. CNRS, UMR7215, France;12. Institut de Myologie, FR-75013 Paris, France;13. INSERM U955, Créteil, France;1. School of Veterinary and Life Sciences, Murdoch University, Perth 6150, Western Australia, Australia;2. Australian Neuro-Muscular Research Institute,CNND, University of Western Australia, Perth 6150, Western Australia, Australia;3. Centre for Medical Research, University of Western Australia, Perth 6150, Western Australia, Australia;4. Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada;5. Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, United Kingdom |
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| Abstract: | ![]()
Cap myopathy is a rare congenital myopathy characterized by the presence of caps within muscle fibres and caused by mutations in ACTA1, TPM2 or TPM3. Thus far, only three cases with TPM3-related cap myopathy have been described. Here, we report on the first autosomal dominant family with cap myopathy in three-generations, caused by a novel heterozygous mutation in the alpha-tropomyosin-slow-encoding gene (TPM3; exon 4; c.445C>A; p.Leu149Ile). The three patients experienced first symptoms of muscle weakness in childhood and followed a slowly progressive course. They presented generalized hypotrophy and mild muscle weakness, elongated face, high arched palate, micrognathia, scoliosis and respiratory involvement. Intrafamilial variability of skeletal deformities, respiratory involvement and mild cardiac abnormalities was noted. Muscle MRI revealed a recognizable pattern of fatty muscle infiltration and masseter muscle hypertrophy. Subsarcolemmal caps were present in 6–10% of the fibres and immunoreactive with anti-tropomyosin antibodies. We conclude that the MRI-pattern of muscle involvement and the presence of masseter muscle hypertrophy in cap myopathy may guide molecular genetic diagnosis towards a mutation in TPM3. Regular respiratory examinations are important, even if patients have no anamnestic clues. We compare our findings to all cases of cap myopathy with identified mutations (n = 11), thus far reported in the literature. |
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| Keywords: | Congenital myopathy Alpha tropomyosin slow Caps Muscle fibre inclusions Genotype–phenotype correlations Whole-body muscle MRI |
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