title: Characterization of glucocerebrosidase in Greek Gaucher disease patients: mutation analysis and biochemical studies.
abstract: Gaucher disease is the most frequent lysosomal storage disease in Greece, accounting for 24% of all lysosomal disorders diagnosed during the last 13 years at the Institute of Child Health in Athens. The nature of the defects in glucocerebrosidase in Greek Gaucher patients with non-neuronopathic (type 1) and neuronopathic (types 2 and 3) phenotypes was investigated at the level of the glucocerebrosidase gene and enzyme activity. Mutation analysis performed in 10/23 Gaucher patients with different types of the disorder led to the identification of four mutations, N370S, L444P, R463C and D409H, comprising 75% of the investigated alleles. N370S was only found in association with type 1 disease. The genotype D409H/R463C was identified for the first time and was associated with the severe type 2 disorder. There was no correlation between residual in vitro enzyme activity and either phenotype or genotype. However, in cultured fibroblast of the neuronopathic cases, glucocerebrosidase protein concentration was reduced and the capacity to degrade exogenous C6NBD-glucosylceramide was more severely impaired.
authors.affiliation: Department of Enzymology and Cellular Function, Children's Hospital Ag. Sophia, Athens, Greece.
authors.forename: H
authors.initials: H
authors.lastname: Michelakakis
authors.forename: E
authors.initials: E
authors.lastname: Dimitriou
authors.forename: S
authors.initials: S
authors.lastname: Van Weely
authors.forename: R G
authors.initials: RG
authors.lastname: Boot
authors.forename: I
authors.initials: I
authors.lastname: Mavridou
authors.forename: M
authors.initials: M
authors.lastname: Verhoek
authors.forename: J M
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D005347:Fibroblasts / Q000201:enzymology; D005776:Gaucher Disease / Q000201:enzymology* / Q000235:genetics; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006115:Greece; D006801:Humans
chemical_list: D004247:DNA; D005962:Glucosylceramidase