Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c

Glycogen storage diseases type 1 (GSD 1) are a group of autosomal recessive disorders characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Mutations of the glucose-6-phosphatase gene are responsible for the most frequent form of GSD 1, the subtype la, while mutations of the glucose-6-phosphate transporter gene (G6PT) have recently been shown to cause the non la forms of GSD, namely the Ib and Ic subtypes, Here, me report on the analysis by single-stranded conformation polymorphism (SSCP) and/or DNA sequencing of the exons of the G6PT in 14 patients diagnosed either as affected by the GSD Ib or Ic subtypes, Mutations in the G6PT gene were found in all patients. Four of the detected mutations were novel mutations, while the others mere previously described. Our results confirm that the GSD Ib and Ic forms are due to mutations in the same gene, i.e. the G6PT gene. We also show that the same kind of mutation can be associated or not with evident clinical complications such as neutrophil impairment. Since no correlation between the type and position of the mutation and the severity of the disease was found, other unknown factors may cause the expression of symptoms, such as neutropenia, which dramatically influence the severity of the disease. (C) 1999 Federation of European Biochemical Societies.