title: 1448C mutation linked to the Pv1.1- genotype in Italian patients with Gaucher disease.
abstract: 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 enzyme-replacement 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.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology-UNIDO, Trieste, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tuteja
authors.forename: B
authors.initials: B
authors.lastname: Bembi
authors.forename: E
authors.initials: E
authors.lastname: Agosti
authors.forename: F E
authors.initials: FE
authors.lastname: Baralle
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005776:Gaucher Disease / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005962:Glucosylceramidase