Molecular genetics of glycogen-storage disease type 1a in Chinese patientsof Taiwan

The mutation spectrum of the glucose 6-phosphatase (G6Pase) gene in Chinese patients with type 1a glycogen-storage disease of Taiwan was studied by PC R/RFLP, temporal temperature gradient gel electrophoresis, and direct DNA s equencing methods. In addition to the two most prevalent mutations, 727G -- > T (44.4%) and R83H (36.1%), that were detected by RFLP analysis, five oth er mutations, 341delG, 933insAA, Q104X, I341N, and H119L were identified. T he frameshift mutations (341delG and 933insAA) and the nonsense mutation (Q 104X) that produce truncated proteins are predicted to be disease-causing. The missense mutation, I341N, occurring in the last transmembrane domain of the ER-bound enzyme, retains a small amount of residual activity of approx imately 10%. Except for R83H, the mutations have been described only in Asi ans. H119L, however, is of particular interest because of the essential rol e of the catalytic histidine of phosphohydrolase. This amino acid is believ ed to be involved in the formation of the phosphoryl-enzyme intermediate du ring catalysis. The patient who was compound heterozygous for 727G -->T and H119L mutations had essentially no G6Pase activity in her liver biopsy. Th is observation is consistent with the importance of H119L in catalysis. (C) 2001 Academic Press.