Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen storage disease type Ia

Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metaboli c disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several di sease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 u nrelated Italian patients. The two most common mutations, R83C and Q347X, a ccounted for 66.9% of the mutant alleles. Eight novel mutations and three r are mutations were identified in 15.7% of disease alleles. These results su ggest that a DNA-based method can be used as an initial screening in Italia n patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable m ethod for the Italian subpopulation coming from Sicily, where the R83C muta tion is present in 80% of mutant alleles. Molecular carrier detection and p renatal diagnosis can be provided to GSD1a families with identified mutatio n in the propositus.