Dominantly inherited distal nemaline/cap myopathy caused by a large deletion in the nebulin gene

Neuromuscul Disord. 2019 Feb;29(2):97-107. doi: 10.1016/j.nmd.2018.12.007. Epub 2018 Dec 20.


We report the first family with a dominantly inherited mutation of the nebulin gene (NEB). This ∼100 kb in-frame deletion encompasses NEB exons 14-89, causing distal nemaline/cap myopathy in a three-generation family. It is the largest deletion characterized in NEB hitherto. The mutated allele was shown to be expressed at the mRNA level and furthermore, for the first time, a deletion was shown to cause the production of a smaller mutant nebulin protein. Thus, we suggest that this novel mutant nebulin protein has a dominant-negative effect, explaining the first documented dominant inheritance of nebulin-caused myopathy. The index patient, a young man, was more severely affected than his mother and grandmother. His first symptom was foot drop at the age of three, followed by distal muscle atrophy, slight hypomimia, high-arched palate, and weakness of the neck and elbow flexors, hands, tibialis anterior and toe extensors. Muscle biopsies showed myopathic features with type 1 fibre predominance in the index patient and nemaline bodies and cap-like structures in biopsies from his mother and grandmother. The muscle biopsy findings constitute a further example of nemaline bodies and cap-like structures being part of the same spectrum of pathological changes.

Keywords: Cap myopathy; Distal myopathy; Dominant nemaline myopathy; Nebulin; Nemaline myopathy-CGH Array.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Humans
  • Male
  • Muscle Proteins / genetics*
  • Muscle, Skeletal / diagnostic imaging*
  • Muscle, Skeletal / pathology
  • Myopathies, Nemaline / diagnosis
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / pathology
  • Pedigree
  • Sequence Deletion
  • Tomography, X-Ray Computed


  • Muscle Proteins
  • nebulin