An unusual ryanodine receptor 1 (RYR1) phenotype: Mild calf-predominant myopathy

Manu Jokela, Giorgio Tasca, Anna Vihola, Eugenio Mercuri, Per-Harald Jonson, Sara Lehtinen, Salla Välipakka, Marika Pane, Maria Donati, Mridul Johari, Marco Savarese, Sanna Huovinen, Pirjo Isohanni, Johanna Palmio, Päivi Hartikainen, Bjarne Udd

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To identify the genetic defect causing a distal calf myopathy with cores.

METHODS: Families with a genetically undetermined calf-predominant myopathy underwent detailed clinical evaluation, including EMG/nerve conduction studies, muscle biopsy, laboratory investigations, and muscle MRI. Next-generation sequencing and targeted Sanger sequencing were used to identify the causative genetic defect in each family.

RESULTS: A novel deletion-insertion mutation in ryanodine receptor 1 (RYR1) was found in the proband of the index family and segregated with the disease in 6 affected relatives. Subsequently, we found 2 more families with a similar calf-predominant myopathy segregating with unique RYR1-mutated alleles. All patients showed a very slowly progressive myopathy without episodes of malignant hyperthermia or rhabdomyolysis. Muscle biopsy showed cores or core-like changes in all families.

CONCLUSIONS: Our findings expand the spectrum of RYR1-related disorders to include a calf-predominant myopathy with core pathology and autosomal dominant inheritance. Two families had unique and previously unreported RYR1 mutations, while affected persons in the third family carried 2 previously known mutations in the same dominant allele.

Original languageEnglish
Pages (from-to)e1600-e1609
JournalNeurology
Volume92
Issue number14
DOIs
Publication statusPublished - Apr 2 2019

Keywords

  • Adolescent
  • Adult
  • Aged
  • Child
  • Creatine Kinase/metabolism
  • Distal Myopathies/genetics
  • Female
  • Humans
  • INDEL Mutation
  • Leg
  • Male
  • Middle Aged
  • Muscle, Skeletal/metabolism
  • Pedigree
  • Ryanodine Receptor Calcium Release Channel/genetics

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