Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing

Am J Med Genet A. 2012 Apr;158A(4):772-8. doi: 10.1002/ajmg.a.35243. Epub 2012 Mar 9.


Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions "nemaline bodies" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM. We have identified recessive RYR1 mutations in a patient with severe congenital NM, through high-throughput screening of congenital myopathy/muscular dystrophy-related genes using massively parallel sequencing with target gene capture. The patient manifested fetal akinesia, neonatal severe hypotonia with muscle weakness, respiratory insufficiency, swallowing disturbance, and ophthalomoplegia. Skeletal muscle histology demonstrated nemaline bodies and small type 1 fibers, but without central cores or minicores. Congenital myopathies, a molecularly, histopathologically, and clinically heterogeneous group of disorders are considered to be a good candidate for massively parallel sequencing.

Publication types

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

MeSH terms

  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Muscle Fibers, Skeletal / pathology
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / pathology
  • Mutation
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / pathology*
  • Ophthalmoplegia / genetics*
  • Ryanodine Receptor Calcium Release Channel / genetics*


  • Ryanodine Receptor Calcium Release Channel