A novel missense mutation (W797R) in the myophosphorylase gene in Spanish patients with McArdle disease

Objective: To investigate the degree of genetic heterogeneity of myophosphorylase deficiency (McArdle disease) in Spain through molecular studies of 10 new patients. Design: The coding sequence of the entire myophosphorylase gene was sequenced in DNA extracted from muscle and blood. Restriction fragment length polymorphism analysis of polymerase chain reaction fragments was used to confirm and simplify detection of a novel mutation. Setting: A collaborative study between 2 university laboratories in Spain and the United States. Results: Five of the 10 patients harbored a novel missense mutation in exon 20, converting a tryptophan to an arginine (W797R). Three patients were homozygous for the ''common" R49X mutation, and the remaining 2 patients were compound heterozygotes for R49X and a previously described missense mutation, G204S. Conclusions: The W797R missense mutation is the third novel mutation to be identified among Spanish patients. Its relative frequency suggests that it should be added to the R49X mutation in the molecular screening of McArdle disease in Spain.