Three new mutations in patients with myophosphorylase deficiency (McArdle disease).

We report three new mutations in patients with myophosphorylase deficiency (McArdle disease). A splice-junction mutation (G-to-A transition at the 5' end of intron 14) and a missense mutation (CTG to CCG at codon 291, changing an encoded leucine to a proline) were identified in Caucasian patients who were heterozygous for a common mutation reported elsewhere (CGA [Arg] to TGA [stop]) at codon 49. The splice-junction mutation destroyed the consensus sequence at the 5' splice site, and a cryptic splice site 67 bp upstream was recognized instead. As a result, there was a 67-bp deletion in the 3'-terminal region of exon 14 in the transcript, resulting in a frameshift with premature translation termination. A deletion of a single codon, 708/709 (TTC, specifying phenylalanine) was identified in Japanese patients. Two affected siblings were homozygotes, and their parents were heterozygotes. A third, unrelated patient was heterozygous for the same mutation, while the myophosphorylase gene on the other allele was only faintly expressed.