Analysis of the beta-glucocerebrosidase gene in Czech and Slovak Gaucher patients: Mutation profile and description of six novel mutant alleles

The aim of this study was to characterize the spectrum of beta-glucocerebro sidase gene mutations in Czech and Slovak Gaucher patients and to study gen otype/phenotype associations. We have analyzed fifty-eight chromosomes from twenty-six type 1, two type 2, and one type 3 beta-glucocerebrosidase defi cient subjects by direct sequencing of PCR products. Fifty-eight mutant all eles were identified. Seventy-eight percent of mutant alleles carried common mutations (N370S 28/ 58, LA44P 11/58, recNciI 5/58, and IVS2(+1)A 1/58), the remaining twenty-tw o percent carried rare and private mutations (1263del55, 1326insT, S196P, r ec(g4889-6506), 203delC, G202E, F216Y, R257X, R120W, R359Q, S107L, LA44P V460V, and D409H + T369M). Six of these alleles have not been previously de scribed (rec(g4889-6506), 1326insT, S196P, G202E, D409H + T369M, and LA44P + 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 mutati ons. The absence of the mutation 84insG that is frequently associated with severe bone disease may have contributed to the low incidence of severe bon e disease in Czech and Slovak Gaucher subjects.