title: Recessive MYPN mutations cause cap myopathy with occasional nemaline rods.
abstract: Congenital myopathies are phenotypically and genetically heterogeneous. We describe homozygous truncating mutations in MYPN in 2 unrelated families with a slowly progressive congenital cap myopathy. MYPN encodes the Z-line protein myopalladin implicated in sarcomere integrity. Functional experiments demonstrate that the mutations lead to mRNA defects and to a strong reduction in full-length protein expression. Myopalladin signals accumulate in the caps together with alpha-actinin. Dominant MYPN mutations were previously reported in cardiomyopathies. Our data uncover that mutations in MYPN cause either a cardiac or a congenital skeletal muscle disorder through different modes of inheritance. Ann Neurol 2017;81:467-473.
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.|National Institute of Health and Medical Research, Illkirch, France.|National Center for Scientific Research, Illkirch, France.|Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.
authors.forename: Xavière
authors.initials: X
authors.lastname: Lornage
authors.affiliation: Sorbonne Universities, Pierre and Marie Curie University, National Institute of Health and Medical Research, National Center for Scientific Research, Center for Research in Myology, Pitié-Salpêtrière Hospital, Paris, France.|Unit of Neuromuscular Morphology, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.|Reference Center for Neuromuscular Pathology Paris-East, Institute of Myology, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Malfatti
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.|National Institute of Health and Medical Research, Illkirch, France.|National Center for Scientific Research, Illkirch, France.|Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.
authors.forename: Chrystel
authors.initials: C
authors.lastname: Chéraud
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.|National Institute of Health and Medical Research, Illkirch, France.|National Center for Scientific Research, Illkirch, France.|Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.|Department of Computer Science, ICube, National Center for Scientific Research, Strasbourg, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.|National Institute of Health and Medical Research, Illkirch, France.|National Center for Scientific Research, Illkirch, France.|Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.|Diagnostic Genetic Laboratory, New Civil Hospital, Regional University Hospital Center, Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Biancalana
authors.affiliation: Department of Neuropediatrics, Reference Center for Neuromuscular Diseases, Roger-Salengro Hospital, Regional University Hospital Center, Lille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.affiliation: Unit of Neuromuscular Morphology, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.|Unit of Neuromuscular Diseases, Department of Neurology, Mental Health, and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.|Neuromuscular Diseases Centre, Department of Clinical Neurosciences, University Hospital of Nice, Nice, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Garibaldi
authors.affiliation: Sorbonne Universities, Pierre and Marie Curie University, National Institute of Health and Medical Research, National Center for Scientific Research, Center for Research in Myology, Pitié-Salpêtrière Hospital, Paris, France.|Reference Center for Neuromuscular Pathology Paris-East, Institute of Myology, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.affiliation: Sorbonne Universities, Pierre and Marie Curie University, National Institute of Health and Medical Research, National Center for Scientific Research, Center for Research in Myology, Pitié-Salpêtrière Hospital, Paris, France.|Unit of Neuromuscular Morphology, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.|Reference Center for Neuromuscular Pathology Paris-East, Institute of Myology, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.affiliation: National Genotyping Center, Genomics Institute, Office of Atomic Energy and Alternative Energies, Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.affiliation: National Genotyping Center, Genomics Institute, Office of Atomic Energy and Alternative Energies, Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Department of Computer Science, ICube, National Center for Scientific Research, Strasbourg, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Thompson
authors.affiliation: Department of Radiology, Neurolocomotor Division, Raymond Poincaré Hospital, University Hospitals Paris-Ile-de-France West, Public Hospital Network of Paris, Garches, France.|Versailles Saint-Quentin-en-Yvelines University, Versailles, France.
authors.forename: Robert-Yves
authors.initials: RY
authors.lastname: Carlier
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.|National Institute of Health and Medical Research, Illkirch, France.|National Center for Scientific Research, Illkirch, France.|Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Sorbonne Universities, Pierre and Marie Curie University, National Institute of Health and Medical Research, National Center for Scientific Research, Center for Research in Myology, Pitié-Salpêtrière Hospital, Paris, France.|Unit of Neuromuscular Morphology, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.|Reference Center for Neuromuscular Pathology Paris-East, Institute of Myology, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.|National Institute of Health and Medical Research, Illkirch, France.|National Center for Scientific Research, Illkirch, France.|Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
mesh_terms: D000328:Adult; D003241:Consanguinity; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree
chemical_list: C426225:MYPN protein, human; D009124:Muscle Proteins