RYR 1 Gene Mutation in Motor Neuron Disease: A 10-Year Case Observation

Motor neuron diseases (MND) are a group of rare, often severe, and life-limiting progressive neurological disorders that primarily affect motor neurons, resulting in muscle weakness and loss of essential muscle functions. Genetic defects play a significant role in MND, contributing to their pathogenesis and progression. The Department of Neurology at Martin Luther University Halle (Germany) followed a male patient with slowly progressive muscle loss, muscle weakness, and muscle pain in the proximal upper arm and shoulder muscles over a period of 10 years and collected clinical, electrophysiological, neuroradiological, laboratory, and genetic data. Clinical neurological and electrophysiological diagnostics clearly indicated MND. A detailed genetic analysis resulted in the first description of an in-frame mutation (heterozygous, c.5691_5693delGGA) in the RYR1 gene (ryanodine receptor 1), which is unknown in MND or RYR1-related neuromuscular disorders. Mutations in RYR1 are associated with various motor disabilities due to muscle weakness. The specific role of RYR1 mutations in the genetic pathogenesis of MND has never been described before and is currently unknown. This case is the first of its kind demonstrating a RYR1 mutation in MND, broadening the spectrum of pathogenetic causes of MND.