Photo Credit: Zbynek Pospisil

The following is a summary of “A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps,” published in the January 2025 issue of Neurology by Segarra-Casas et al.     

Pathogenic variants in the RYR1 gene have been associated with various conditions, from congenital myopathy to adult manifestations, including exercise intolerance and muscle cramps.  

Researchers conducted a retrospective study to investigate the clinical correlation of the p.Leu2286Val variant in the RYR1 gene in people from the Basque Country.  

They performed clinical evaluations, including muscle magnetic resonance imaging (MRI), electromyography (EMG), and muscle biopsy on families carrying the p.Leu2286Val variant. They analyzed haplotypes using available people and their relatives.  

The results showed that people with the p.Leu2286Val variant in the Basque population shared a common haplotype, indicating a founder effect. The most common features were exertional myalgia, high creatine kinase (CK) levels, cramps, and muscle hypertrophy. None of the people with only the p.Leu2286Val variant showed progression to severe muscle weakness. Muscle MRI revealed heterogeneous muscle involvement, and muscle biopsy showed non-specific findings in 2 people. While 1 person with only the p.Leu2286Val variant exhibited features of the central core disease, 2 people with an additional RYR1 variant showed a more severe phenotype.  

They concluded that in affected people p.Leu2286Val variant in the RYR1 gene was associated with a milder phenotype of exercise intolerance, myalgia, and hyperCKemia .  

Source: onlinelibrary.wiley.com/doi/full/10.1111/ene.16471