MUTATIONS IN THE PHOSPHORYLASE-KINASE GENE PHKA2 ARE RESPONSIBLE FOR X-LINKED LIVER-GLYCOGEN STORAGE DISEASE

Phosphorylase kinase (PHK) is a key enzyme in the control of glycogen breakdown. Several types of PHK deficiency have been described of which X-linked liver glycogenosis type I (XLG I) is the most common, Since the XLG I locus and the gene encoding the liver a-subunit gene of PHK (PHKA2) have both been localized to Xp22, PHKA2 was a candidate gene for XLG I. In this study we identified four point mutations in four unrelated XLG I patients: three mutations introduce a premature stop codon, whereas the fourth mutation abolishes a splice site consensus sequence leading to exon skipping, These findings indicate that PHKA2 is the XLG I gene.