Two homozygous mutations (R193W and 794/795 delAA) in the myophosphorylase gene in a patient with McArdle's disease.

We report two novel homozygous mutations in the myophosphorylase gene (PYGM) in a patient with McArdle's disease. A C-to-T transition that changed an arginine to tryptophan at codon 193 (R193W) in exon 5, and a deletion of two adenine base pairs in exon 20 at codon 794/795 (794/795 delAA) were identified. Several lines of evidence suggest the pathogenicity of both mutations: (i) they were the only nucleotide alteration in the coding region and adjacent exon/intron boundaries of the PYGM gene; (ii) the R193W mutation leads to the replacement of a highly conserved amino acid residue involved in glucose-6-P binding, and the 794/795 delAA mutation predicts a frameshift and premature termination of the protein; (iii) 60 normal controls and 20 disease controls did not have the mutations in their 160 alleles. Hum Mutat 15:294, 2000.