Analysis of the beta-glucocerebrosidase gene in Czech and Slovak Gaucher patients: mutation profile and description of six novel mutant alleles
Language English Country United States Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
10744424
PII: S1079979699902565
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- White People genetics MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Gene Frequency MeSH
- Gaucher Disease epidemiology ethnology genetics MeSH
- Genetic Variation MeSH
- Genotype MeSH
- Glucosylceramidase deficiency genetics MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation genetics MeSH
- DNA Mutational Analysis MeSH
- Child, Preschool MeSH
- Aged MeSH
- Blotting, Southern MeSH
- Jews genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Slovakia epidemiology MeSH
- Names of Substances
- Glucosylceramidase MeSH
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.
Long-Term Evaluation of Biomarkers in the Czech Cohort of Gaucher Patients