Novel ACTA1 mutation causes late-presenting nemaline myopathy with unusual dark cores

Matteo Garibaldi, Fabiana Fattori, Elena Maria Pennisi, Gioia Merlonghi, Laura Fionda, Fiammetta Vanoli, Luca Leonardi, Elisabetta Bucci, Stefania Morino, Andrea Micaloni, Tommaso Tartaglione, Bas Uijterwijk, Martijn Zierikzee, Coen Ottenheijm, Enrico Silvio Bertini, Antonella Stoppacciaro, Salvatore Raffa, Marco Salvetti, Giovanni Antonini

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


ACTA1 gene encodes the skeletal muscle alpha-actin, the core of thin filaments of the sarcomere. ACTA1 mutations are responsible of several muscle disorders including nemaline, cores, actin aggregate myopathies and fiber-type disproportion. We report clinical, muscle imaging, histopatological and genetic data of an Italian family carrying a novel ACTA1 mutation. All affected members showed a late-presenting, diffuse muscle weakness with sternocleidomastoideus and temporalis atrophy. Mild dysmorphic features were also detected. The most affected muscles by muscle MRI were rectus abdominis, gluteus minimus, vastus intermedius and both gastrocnemii. Muscle biopsy showed the presence of nemaline bodies with several unusual dark areas at Gomori Trichrome, corresponding to unstructured cores with abundant electrodense material by electron microscopy. The molecular analysis revealed missense variant c.148G>A; p.(Gly50Ser) in the exon 3 of ACTA1, segregating with affected members in the family. We performed a functional essay of fibre contractility showing a higher pCa50 (a measure of the calcium sensitivity of force) of type 1 fibers compared to control subjects’ type 1 muscle fibers. Our findings expand the clinico-pathological spectrum of ACTA1-related congenital myopathies and the genetic spectrum of core-rod myopathies.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalNeuromuscular Disorders
Issue number2
StatePublished - Feb 2021
Externally publishedYes


  • Acta1
  • Central core
  • Central core disease
  • Congenital myopathy
  • Core-rod myopathy
  • Nemaline myopathy

ASJC Scopus subject areas

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


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