Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods

Sandra Donkervoort, Sophelia H.S. Chan, Leslie H. Hayes, Nathaniel Bradley, David Nguyen, Meganne E. Leach, Payam Mohassel, Ying Hu, Mathula Thangarajh, Diana Bharucha-Goebel, Amanda Kan, Ronnie S.L. Ho, Christine A. Reyes, Jessica Nance, Steven A. Moore, A. Reghan Foley, Carsten G. Bönnemann

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.

Original languageEnglish (US)
Pages (from-to)531-536
Number of pages6
JournalNeuromuscular Disorders
Issue number6
StatePublished - Jun 2017


  • ACTA1
  • Congenital myopathies
  • Cytoplasmic bodies
  • Skeletal muscle α-actin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


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