Reports: Human muscle glycogenosis due to phosphorylase kinase deficiency associated with a nonsense mutation in the muscle isoform of the α 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, adultonset Phk deficiency. The coding sequences of three candidate genes were analyzed by RT-PCR and sequencing: the muscle Isoform of the α subunit (α_M), a muscle-specifically expressed exon of the β subunit, and the muscle Isoform of the y subunit. Whereas the latter two sequences were found to be normal, we identified a nonsense mutation in α_M. The condition of this patient therefore is a human homolog of the Xlinked muscle Phk deficiency of I-strain mice. To our knowledge, this is the first description of a human Phk deficiency mutation.