Recessive MYPN mutations cause cap myopathy with occasional nemaline rods

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


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.

MeSH terms

  • Adult
  • Consanguinity
  • Exome
  • Female
  • Humans
  • Male
  • Muscle Proteins / genetics*
  • Mutation
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / physiopathology
  • Pedigree


  • MYPN protein, human
  • Muscle Proteins

Supplementary concepts

  • Cap Myopathy