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 several forms of glycogen storage disease in humans and animals that differ in mode of inheritance and tissue-specificity. Mutations affecting different subunits and isoforms of Phk are expected to contribute to this heterogeneity. In the present study, we have investigated a case of muscle-specific, adult-onset Phk deficiency. The coding sequences of three candidate genes were analyzed by RT-PCR and sequencing: the muscle isoform of the alpha subunit (alpha M), a muscle-specifically expressed exon of the beta subunit, and the muscle isoform of the gamma subunit. Whereas the latter two sequences were found to be normal, we identified a nonsense mutation in alpha M. The condition of this patient therefore is a human homolog of the X-linked muscle Phk deficiency of I-strain mice. To our knowledge, this is the first description of a human Phk deficiency mutation.