title: Analysis of the beta-glucocerebrosidase gene in Czech and Slovak Gaucher patients: mutation profile and description of six novel mutant alleles.
abstract: The aim of this study was to characterize the spectrum of 13-glucocerebrosidase gene mutations in Czech and Slovak Gaucher patients and to study genotype/phenotype associations. We have analyzed fifty-eight chromosomes from twenty-six type I, two type 2, and one type 3 13-glucocerebrosidase deficient subjects by direct sequencing of PCR products. Fifty-eight mutant alleles were identified. Seventy-eight percent of mutant alleles carried common mutations (N370S 28/58, L444P 11/58, recNciI 5/58, and IVS2(+1)A 1/58), the remaining twenty-two percent carried rare and private mutations (1263del55, l326insT, S196P, rec(g4889-6506), 2O3delC, G202E, F216Y, R257X, R12OW, R359Q, S1O7L, L444P + V460V, and D409H + T369M). Six of these alleles have not been previously described (rec(g4889-6506), 1326insT, SI96P. G202E, D409H + T369M, and L444P + V460V). The most common genotypes were N370S/L444P (8/29). N370S/recNciI (5/29), and N370S/N370S (2/29). The spectrum of the mutations is characteristic for a Caucasian (non-Jewish) population, with N370S, L444P and recNciI being the most prevalent mutations. The absence of the mutation 84insG that is frequently associated with severe bone disease may have contributed to the low incidence of severe bone disease in Czech and Slovak Gaucher subjects.
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University, 1st Faculty of Medicine, Ke Karlovu 2. 12000 Prague 2, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Hodanová
authors.forename: M
authors.initials: M
authors.lastname: Hrebícek
authors.forename: M
authors.initials: M
authors.lastname: Cervenková
authors.forename: L
authors.initials: L
authors.lastname: Mrázová
authors.forename: L
authors.initials: L
authors.lastname: Vepreková
authors.forename: J
authors.initials: J
authors.lastname: Zemen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D018153:Czech Republic / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D005776:Gaucher Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005962:Glucosylceramidase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007223:Infant; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D018154:Slovakia / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D005962:Glucosylceramidase