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Ann Neurol. 2017 Mar;81(3):467-473. doi: 10.1002/ana.24900. Epub 2017 Mar 20.

Recessive MYPN mutations cause cap myopathy with occasional nemaline rods.

Lornage X1,2,3,4, Malfatti E5,6,7, Chéraud C1,2,3,4, Schneider R1,2,3,4,8, Biancalana V1,2,3,4,9, Cuisset JM10, Garibaldi M6,11,12, Eymard B5,7, Fardeau M5,6,7, Boland A13, Deleuze JF13, Thompson J8, Carlier RY14,15, Böhm J1,2,3,4, Romero NB5,6,7, Laporte J1,2,3,4.

Author information

1
Institute of Genetics and Molecular and Cellular Biology, Illkirch, France.
2
National Institute of Health and Medical Research, Illkirch, France.
3
National Center for Scientific Research, Illkirch, France.
4
Strasbourg Federation of Translational Medicine, University of Strasbourg, Illkirch, France.
5
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.
6
Unit of Neuromuscular Morphology, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.
7
Reference Center for Neuromuscular Pathology Paris-East, Institute of Myology, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France.
8
Department of Computer Science, ICube, National Center for Scientific Research, Strasbourg, France.
9
Diagnostic Genetic Laboratory, New Civil Hospital, Regional University Hospital Center, Strasbourg, France.
10
Department of Neuropediatrics, Reference Center for Neuromuscular Diseases, Roger-Salengro Hospital, Regional University Hospital Center, Lille, France.
11
Unit of Neuromuscular Diseases, Department of Neurology, Mental Health, and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
12
Neuromuscular Diseases Centre, Department of Clinical Neurosciences, University Hospital of Nice, Nice, France.
13
National Genotyping Center, Genomics Institute, Office of Atomic Energy and Alternative Energies, Evry, France.
14
Department of Radiology, Neurolocomotor Division, Raymond Poincaré Hospital, University Hospitals Paris-Ile-de-France West, Public Hospital Network of Paris, Garches, France.
15
Versailles Saint-Quentin-en-Yvelines University, Versailles, France.

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.

PMID:
28220527
DOI:
10.1002/ana.24900
[Indexed for MEDLINE]

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