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 Citations (Scopus)

Abstract

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
Volume5
Issue number3
DOIs
StatePublished - Jan 1 2017

Fingerprint

Congenital Structural Myopathies
Mitochondrial Myopathies
Exome
Central Core Myopathy
Myotonia Congenita
Joint Instability
Ophthalmoplegia
Ryanodine Receptor Calcium Release Channel
Muscle Hypotonia
Scoliosis
Muscular Diseases
Respiratory Insufficiency
Spine
Hypertension
Bone and Bones

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Whole exome sequencing of a patient with suspected mitochondrial myopathy reveals novel compound heterozygous variants in RYR1. / Blackburn, Patrick R.; Selcen, Duygu; Gass, Jennifer M.; Jackson, Jessica L.; Macklin, Sarah; Cousin, Margot A.; Boczek, Nicole J.; Klee, Eric W; Dimberg, Elliot L.; Kennelly, Kathleen; Atwal, Paldeep S.

In: Molecular Genetics and Genomic Medicine, Vol. 5, No. 3, 01.01.2017, p. 295-302.

Research output: Contribution to journalArticle

Blackburn, Patrick R. ; Selcen, Duygu ; Gass, Jennifer M. ; Jackson, Jessica L. ; Macklin, Sarah ; Cousin, Margot A. ; Boczek, Nicole J. ; Klee, Eric W ; Dimberg, Elliot L. ; Kennelly, Kathleen ; Atwal, Paldeep S. / Whole exome sequencing of a patient with suspected mitochondrial myopathy reveals novel compound heterozygous variants in RYR1. In: Molecular Genetics and Genomic Medicine. 2017 ; Vol. 5, No. 3. pp. 295-302.
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