Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

Eur J Hum Genet. 2015 Jun;23(6):883-6. doi: 10.1038/ejhg.2014.169. Epub 2014 Sep 3.


Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / genetics*
  • Actins / metabolism
  • Adult
  • Amino Acid Sequence
  • Genes, Recessive
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation, Missense*
  • Myopathies, Structural, Congenital / diagnosis
  • Myopathies, Structural, Congenital / genetics*
  • Polymorphism, Single Nucleotide
  • Siblings
  • Spine / pathology*


  • Actins