1448C mutation linked to the Pv1 patients with Gaucher disease

Gaucher disease is the most common of the glycolipid storage diseases and is caused by an inherited deficiency of the enzyme glucocerebrosidase. It is a very heterogeneous disease and presents early and late onset forms which may or may not be associated with a neurological disease. Several point mutations of the glucocerebrosidase gene have been reported to cause this disease. This is the first report of the mutations causing GD in Italy. In this study often patients of non-Jewish origin, two mutations (1226G and 1448C) accounted for 19 of 20 disease alleks. In these patients a gene frequency of 33% for the 1226G mutation and 57.8% for the 1448C mutation was found. The patients homozygous for the 1448C mutation were also homozygous for the Pvl-1~ genotype (polymorphic Pvu II site present at nt. 3931). This is in contrast with previous reports Unking 1448C mutation to the Pvl*l+ genotype. Two out of the three 1448C homozygous patients are currently free of any evident neurological symptoms. These patients have been undergoing enzymereplacement therapy for the last one year and have a Pvl-l~/1448C glucocerebrosidase haplotype. Both these factors appear to be associated with a late development of neuronopathic disease.