An unusual ryanodine receptor 1 (RYR1) phenotype: Mild calf-predominant myopathy. (2nd April 2019)

• Record Type: Journal Article
• Authors: Jokela, Manu; Tasca, Giorgio; Vihola, Anna; Mercuri, Eugenio; Jonson, Per-Harald; Lehtinen, Sara; Välipakka, Salla; Pane, Marika; Donati, Maria; Johari, Mridul; Savarese, Marco; Huovinen, Sanna; Isohanni, Pirjo; Palmio, Johanna; Hartikainen, Päivi; Udd, Bjarne
• Is Part Of: Neurology. Volume 92:Number 14(2019)
• Publication Date: 2019-04-02
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000007246
• Languages: English
• ISSNs: 0028-3878

Abstract

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.