CHARACTERIZATION OF GLUCOCEREBROSIDASE IN GREEK GAUCHER DISEASE PATIENTS - MUTATION ANALYSIS AND BIOCHEMICAL-STUDIES

Gaucher disease is the most frequent lysosomal storage disease in Gree ce, 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 no n-neuronopathic (type 1) and neuronopathic (types 2 and 3) phenotypes was investigated at the level of the glucocerebrosidase gene and enzym e activity. Mutation analysis performed in 10/23 Gaucher patients with different types of the disorder led to the identification of four mut ations, N370S, L444P, R463C and D409H, comprising 75% of the investiga ted alleles. N370S was only found in association with type I disease. The genotype D409H/R463C was identified for the first time and was ass ociated with the severe type 2 disorder. There was no correlation betw een residual in vitro enzyme activity and either phenotype or genotype . However, in cultured fibroblasts of the neuronopathic cases, glucoce rebrosidase protein concentration was reduced and the capacity to degr ade exogenous C6NBD-glucosylceramide was more severely impaired.