HUMAN MUSCLE GLYCOGENOSIS DUE TO PHOSPHORYLASE-KINASE DEFICIENCY ASSOCIATED WITH A NONSENSE MUTATION IN THE MUSCLE ISOFORM OF THE ALPHA-SUBUNIT

Heritable phosphorylase kinase (Phk) deficiency is responsible for sev eral forms of glycogen storage disease in humans and animals that diff er in mode of inheritance and tissue-specificity. Mutations affecting different subunits and isoforms of Phk are expected to contribute to t his heterogeneity. In the present study, we have investigated a case o f muscle-specific, adult-onset Phk deficiency. The coding sequences of three candidate genes were analyzed by RT-PCR and sequencing: the mus cle isoform of the alpha subunit (alpha(M)), a muscle-specifically exp ressed exon of the beta subunit, and the muscle isoform of the gamma s ubunit. Whereas the latter two sequences were found to be normal, we i dentified a nonsense mutation in alpha(M) The condition of this patien t therefore is a human homolog of the X-linked muscle Phk deficiency o f I-strain mice. To our knowledge, this is the first description of a human Phk deficiency mutation.