title: Glucocerebrosidase genotype of Gaucher patients in The Netherlands: limitations in prognostic value.
abstract: Gaucher disease is a recessively inherited lysosomal storage disorder that is caused by a deficiency in glucocerebrosidase activity. The clinical expression is markedly heterogeneous with respect to age of onset, progression, severity, and neurological involvement. The relative incidence of glucocerebrosidase (GC) mutations has been studied extensively for Jewish but not for non-Jewish Caucasian patient populations. The present survey on mutant GC genotypes prevalent in Gaucher disease in The Netherlands was taken of 72 patients from different genetic backgrounds. This number is more than half the total number of affected Gaucher patients to be expected on the basis of the incidence of the disorder in this country. Analysis of nine GC mutations led to the identification of 74% of the mutant GC alleles in patients from 44 unrelated Dutch families (i.e., families that have lived in The Netherlands for at least several generations) and of 44% of the mutant GC alleles in patients from nine unrelated families that recently immigrated from both European and non-European countries. The N370S (cDNA 1226G) GC mutation proved to occur most frequently (41%) in the unrelated Dutch patients and less frequently (6%) in the unrelated immigrant patients and was always associated with the nonneuronopathic (Type 1) form of the disease. Apart from the association of the N370S mutation with Type 1 Gaucher disease, the prognostic value of GC genotyping was limited, since a particular GC genotype did not correlate closely to a specific clinical course, or to a specific relative responsiveness to enzyme-supplementation therapy.
authors.affiliation: Department of Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Boot
authors.forename: C E
authors.initials: CE
authors.lastname: Hollak
authors.forename: M
authors.initials: M
authors.lastname: Verhoek
authors.forename: P
authors.initials: P
authors.lastname: Sloof
authors.forename: B J
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: W J
authors.initials: WJ
authors.lastname: Kleijer
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: M H
authors.initials: MH
authors.lastname: van Oers
authors.forename: M M
authors.initials: MM
authors.lastname: Mannens
authors.forename: J M
authors.initials: JM
authors.lastname: Aerts
authors.forename: S
authors.initials: S
authors.lastname: van Weely
mesh_terms: D015139:Blotting, Southern; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D005838:Genotype; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D009426:Netherlands; D010375:Pedigree; D011379:Prognosis
chemical_list: D005962:Glucosylceramidase