July 24, 2018; 91 (4) Article
A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine
Macarena Cabrera-Serrano, Fabiola Mavillard, Valerie Biancalana, Eloy Rivas, Bharti Morar, Aurelio Hernández-Laín, Montse Olive, Nuria Muelas, Eduardo Khan, Alejandra Carvajal, Pablo Quiroga, Jordi Diaz-Manera, Mark Davis, Rainiero Ávila, Cristina Domínguez, Norma Beatriz Romero, Juan J. Vílchez, David Comas, Nigel G. Laing, Jocelyn Laporte, Luba Kalaydjieva, Carmen Paradas
First published June 27, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005862
Macarena Cabrera-Serrano
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Fabiola Mavillard
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Valerie Biancalana
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Eloy Rivas
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Bharti Morar
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Aurelio Hernández-Laín
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Montse Olive
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Nuria Muelas
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Eduardo Khan
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Alejandra Carvajal
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Pablo Quiroga
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Jordi Diaz-Manera
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Mark Davis
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Rainiero Ávila
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Cristina Domínguez
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Norma Beatriz Romero
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Juan J. Vílchez
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
David Comas
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Nigel G. Laing
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Jocelyn Laporte
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Luba Kalaydjieva
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
Carmen Paradas
From the Unidad de Enfermedades Neuromusculares, Department of Neurology (M.C.-S., C.P.), Instituto de Biomedicina de Sevilla (IBiS) (M.C.-S., F.M., C.P.), and Department of Pathology, Neuropathology Unit (E.R.), Hospital Universitario Virgen del Rocío, Sevilla, Spain; Laboratoire Diagnostic Génétique (V.B.), Faculté de Médecine–CHRU, Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) (V.B., R.Á., J.L.), Illkirch, France; Harry Perkins Institute of Medical Research and Centre for Medical Research (B.M., N.G.L., L.K.), University of Western Australia, Nedlands; Department of Pathology (Neuropathology) (A.H.-L.), Hospital Universitario 12 de Octubre, Madrid Research Institute; Neuropathology Unit (M.O.), Department of Pathology and Neuromuscular Unit, Department of Neurology, IDIBELL–Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona; Department of Neurology and IIS La Fe (N.M., J.J.V.), Hospital Universitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.M., J.D.-M., J.J.V.); Department of Neurology (E.K.), Consulta de Enfermedades Neuromusculares y Unidad de ELA, Hospital General Universitario Santa Lucía, Cartagena, Murcia; Department of Neurology (A.C.), Hospital Virgen de las Nieves, Granada; Department of Neurology (P.Q.), Hospital Torrecárdenas, Almería; Unidad de Enfermedades Neuromusculares (J.D.-M.), Department of Neurology, Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Diagnostic Genomics (M.D.), PathWest Laboratory Medicine WA, Perth, Australia; Department of Neurology (C.D.), Hospital 12 de Octubre, Madrid, Spain; Unité de Morphologie Neuromusculaire (N.B.R.), Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris; Université Sorbonne (N.B.R.), UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France; Department of Medicine (J.J.V.), Universitat de Valencia; Department of Experimental and Health Sciences (D.C.), Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain; Centre National de la Recherche Scientifique (J.L.), UMR7104, Illkirch; and Institut National de la Santé et de la Recherche Médicale (J.L.), U964, Illkirch, France.
A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine
Macarena Cabrera-Serrano, Fabiola Mavillard, Valerie Biancalana, Eloy Rivas, Bharti Morar, Aurelio Hernández-Laín, Montse Olive, Nuria Muelas, Eduardo Khan, Alejandra Carvajal, Pablo Quiroga, Jordi Diaz-Manera, Mark Davis, Rainiero Ávila, Cristina Domínguez, Norma Beatriz Romero, Juan J. Vílchez, David Comas, Nigel G. Laing, Jocelyn Laporte, Luba Kalaydjieva, Carmen Paradas
Neurology Jul 2018, 91 (4) e339-e348; DOI: 10.1212/WNL.0000000000005862
Citation Manager Formats
Make Comment
See Comments
Downloads
158
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective To describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified.
Methods Patients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed.
Results Eighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BIN1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confirmed all families are related. In addition to clinical features typical of CNM, such as proximal limb weakness and ophthalmoplegia, most patients in our cohort presented with prominent axial weakness, often associated with rigid spine. Severe fat replacement of paravertebral muscles was demonstrated by muscle imaging. This phenotype seems to be specific to the p.Arg234Cys mutation, not reported in other BIN1 mutations. Extreme clinical variability was observed in the 2 compound heterozygous patients for the p.Arg234Cys/p.Arg145Cys mutations, from a congenital onset with catastrophic outcome to a late-onset disease. Screening of European Roma controls (n = 758) for the p.Arg234Cys variant identified a carrier frequency of 3.5% among the Spanish Roma.
Conclusion We have identified a BIN1 founder Roma mutation associated with a highly specific phenotype, which is, from the present cohort, the main cause of CNM in Spain.
Glossary
- cDNA=
- complementary DNA;
- CNM=
- centronuclear myopathy;
- DM1=
- myotonic dystrophy type I;
- NGS=
- next-generation sequencing;
- SDH=
- succinate dehydrogenase
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received December 17, 2017.
- Accepted in final form April 16, 2018.
- © 2018 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
No comments have been published for this article.
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Advertisement
Related Articles
- No related articles found.
Topics Discussed
Alert Me
Recommended articles
-
Clinical/Scientific Notes
PHENOTYPE OF A PATIENT WITH RECESSIVE CENTRONUCLEAR MYOPATHY AND A NOVEL BIN1 MUTATIONK. G. Claeys, T. Maisonobe, J. Böhm et al.Neurology, February 08, 2010 -
Resident and Fellow Section
Clinical Reasoning: A 51-year-old woman with weakness and stiff neckCharles D. Kassardjian, Margherita Milone et al.Neurology, July 27, 2015 -
Research Articles
Spectrum of Clinical Features in X-Linked Myotubular Myopathy CarriersAn International Questionnaire StudyStacha F.I. Reumers, Frederik Braun, Jennifer E. Spillane et al.Neurology, May 19, 2021 -
Article
Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathyOzge Ceyhan-Birsoy, Pankaj B. Agrawal, Carlos Hidalgo et al.Neurology, August 23, 2013