An Italian team reports the observations of two unrelated men, aged 30 and 39 years, complaining of muscle stiffness after sustained physical activity or exposure to cold accompanied by elevated CPK levels.
- Muscle biopsy revealed the presence of submembranous tubular aggregates in type 2 fibers, without any other histological abnormality, especially of the core type.
- After exclusion of a mutation in the coding sequences of the STIM1, ORAI1 and CASQ1 genes, a new generation sequencing targeting a panel of 20 genes involved in excitation-contraction coupling allowed the identification of two mutations in the RYR1 gene: the c.6617C>T mutation in exon 40 and the c.7300G>A mutation in exon 45, two variants considered as pathogenic in malignant hyperthermia
