A1 Refereed original research article in a scientific journal

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




AuthorsJokela M., Tasca G., Vihola A., Mercuri E., Jonson P., Lehtinen S., Välipakka S., Pane M., Donati M., Johari M., Savarese M., Huovinen S., Isohanni P., Palmio J., Hartikainen P., Udd B.

Publication year2019

JournalNeurology

Journal name in sourceNeurology

Volume92

Issue14

First page E1600

Last pageE1609

ISSN1526-632X

eISSN1526-632X

DOIhttps://doi.org/10.1212/WNL.0000000000007246

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/40494259


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.


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