Epidemiologia molecolare della glicogenosi tipo la nella casistica italiana: Possibilità di diagnosi non invasiva e prevenzione

Diagnosis of glycogen storage disease type 1a (GSD type 1a) currently is established by demonstrating the lack of glucose-6-phosphatase (G6P-ase) in patient's biopsied liver specimen. Recent cloning of the G6P-ase cDNA and identification of mutations in the G6P-ase gene that cause GSD type 1a allow for a non invasive diagnosis. A diagnostic method based on mutation analyses need a rapide screening method for detecting the majority of these mutations and the prevalent mutations in different ethnic/racial group. In the present report we have examined the G6P-ase gene of 43 Italian patients with GSD type 1a, 36 of them with enzimatically confirmed diagnosis and 7 with clinical diagnosis. Using SSCP analysis we detected four mutations in 72.1% of mutated alleles. R83C (44.1%) and Q347X (23.2%) are the must prevalent mutations. The R295C rare mutation was identified in two compound heterozygotes. The mutation S298P is a new mutation, confirmed by direct sequencing, identified in a homozygous patient born to related parents. Of the 43 patients analyzed, 7 contained no identifiable mutant alleles, 10 contained only one mutant allele and 26 contained two mutant alleles (17 homozygotes and 9 compound heterozygotes). Our results demonstrate that two mutations, R83C and Q347X, are the major cause of GSD type 1a in Italy and, moreover, that the patients of Sicilian origin have mostly R83C mutation (10/11 known alleles). A DNA based diagnosis can be used as an initial screening for Italian patients clinically suspected of have GSD type 1a, overall, if they come from Sicily. The knowledge of the genotype may be applicable to carrier detection and prenatal diagnosis.