Whole exome sequencing of a patient with suspected mitochondrial myopathy reveals novel compound heterozygous variants in RYR1

Patrick R. Blackburn, Duygu Selcen, Jennifer M. Gass, Jessica L. Jackson, Sarah Macklin, Margot A. Cousin, Nicole J. Boczek, Eric W Klee, Elliot L. Dimberg, Kathleen Kennelly, Paldeep S. Atwal

Research output: Contribution to journalArticle

4 Scopus citations


Background: Pathogenic variants in ryanodine receptor 1 (RYR1, MIM# 180901) are the cause of congenital myopathy with fiber-type disproportion, malignant hyperthermia susceptibility type 1, central core disease of muscle, multiminicore disease and other congenital myopathies. Methods: We present a patient with global developmental delay, hypotonia, myopathy, joint hypermobility, and multiple other systemic complaints that were noted early in life. Later she was found to have multiple bone deformities involving her spine, with severe scoliosis that was corrected surgically. She was also diagnosed with ophthalmoplegia, chronic hypercapnic respiratory failure, and hypertension. At 22 years of age she presented to the genetics clinic with a diagnosis of mitochondrial myopathy and underwent whole exome sequencing (WES). Results: Whole exome sequencing revealed two novel compound heterozygous variants in RYR1 (c.7060_7062del, p.Val2354del and c.4485_4500del, p.Tyr1495X). Conclusion: Review of her clinical, pathologic, and genetic findings pointed to a diagnosis of a congenital myopathy with fiber-type disproportion.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalMolecular Genetics and Genomic Medicine
Issue number3
StatePublished - Jan 1 2017



  • CFTD
  • congenital fiber-type disproportion
  • congenital myopathy
  • malignant hyperthermia
  • ryanodine receptor 1
  • RYR1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this