Journal of Inherited Metabolic Disease

, Volume 18, Issue 5, pp 609–615

Characterization of glucocerebrosidase in Greek Gaucher disease patients: mutation analysis and biochemical studies

  • H. Michelakakis
  • E. Dimitriou
  • S. Van Weely
  • R. G. Boot
  • I. Mavridou
  • M. Verhoek
  • J. M. F. G. Aerts
Article

DOI: 10.1007/BF02436006

Cite this article as:
Michelakakis, H., Dimitriou, E., Van Weely, S. et al. J Inherit Metab Dis (1995) 18: 609. doi:10.1007/BF02436006

Summary

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 residualin vitro enzyme activity and either phenotype or genotype. However, in cultured fibroblasts of the neuronopathic cases, glucocerebrosidase protein concentration was reduced and the capacity to degrade exogenous C6NBD-glucosylceramide was more severely impaired.

Copyright information

© Society for the Study of Inborn Errors of Metabolism and Kluwer Academic Publishers 1995

Authors and Affiliations

  • H. Michelakakis
    • 1
  • E. Dimitriou
    • 1
  • S. Van Weely
    • 2
  • R. G. Boot
    • 2
  • I. Mavridou
    • 1
  • M. Verhoek
    • 2
  • J. M. F. G. Aerts
    • 2
  1. 1.Department of Enzymology and Cellular Function, Institute of Child HealthChildren's Hospital ‘Ag. Sophia’AthensGreece
  2. 2.E. C. Slater InstituteUniversity of AmsterdamThe Netherlands