© 1993 Oxford University Press
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1448C mutation linked to the Pv1. 1– genotype in Italian patients with Gaucher disease
International Centre for Genetic Engineering and Biotechnology-UNIDO Padriciano 99, Area Science Park, 34012 Trieste 1Istituto Burlo Garofolo of Trieste Via dell'lstria, 65/1, 34145 Trieste, Italy
* To whom correspondence should be addressed
Received December 21, 1992; Revised March 31, 1993; Accepted March 31, 1993
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 of ten patients of non-Jewish origin, two mutations (1226G and 1448C) accounted for 19 of 20 disease alleles. 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 Pv1.1– genotype (polymorphic Pvu II site present at nt. 3931). This is in contrast with previous reports linking 1448C mutation to the Pv1.1+ 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 Pv1.1–/1448C glucocerebrosidase haplotype. Both these factors appear to be associated with a late development of neuronopathic disease.