Genotype-phenotype correlations in recessive RYR1-related myopathies

Kimberly Amburgey, Angela Bailey, Jean H Hwang, Mark A Tarnopolsky, Carsten G Bonnemann, Livija Medne, Katherine D Mathews, James Collins, Jasper R Daube, Gregory P Wellman, Brian Callaghan, Nigel F Clarke, James J Dowling

RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed.