McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases

McArdle's disease is an inherited disease that results froma lack of functional muscle glycogen phosphorylase. We reporthere the identification of a C to T transition in exon 1 ofthe muscle phosphorylase gene found in all patients studied.This base pair mutation results in the substitution of a stopcodon (TGA) for the codon (CGA) for Arg49 in the mature protein,and generates a novel restriction site for Niaill. Of sixteenMcArdle's patients, ten are homozygous for this mutation; theremainder are heterozygous. Additional unidentified mutationsmust lead to the McArdle's phenotype in the latter group ofpatients.