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

15 Citations (Scopus)


ObjectiveTo identify the genetic defect causing a distal calf myopathy with cores.MethodsFamilies 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.ResultsA 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.ConclusionsOur 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
Issue number14
Publication statusPublished - 2 Apr 2019
Externally publishedYes


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