MOLECULAR ANALYSIS OF GAUCHER-DISEASE - DISTRIBUTION OF 8 MUTATIONS AND THE COMPLETE GENE DELETION IN 27 PATIENTS FROM GERMANY

Gaucher disease is the most common lysosomal storage disease with a hi gh prevalence in the Ashkenazi Jewish population but it is also presen t in other populations. The presence of eight mutations (1226G, 1448C, IVS2+1, 84GG, 1504T. 1604T, 1342C and 1297T) and the complete deletio n of the beta-glucocerebrosidase gene was investigated in 25 unrelated non-Jewish patients with Gaucher's disease in Germany. In the Jewish population, three of these mutations account for mon than 90% of all m utated alleles. In addition, relatives of two patients were included i n our study. Restriction fragment length polymorphism analysis and seq uencing of PCR products obtained from DNA of peripheral blood leukocyt es was performed for mutation analysis. Gene deletion was detected by comparison of radioactively labelled PCR fragments of both the functio nal beta-glucocerebrosidase gene and the pseudogene. Among the unrelat ed patients, 50 alleles were investigated and the mutations identified in 35 alleles (70%), whereas 15 alleles (30%) remained unidentified. The most prevalent mutation in our group of patients was the 1226G (37 0(Asn-->Ser)) mutation, accounting for 18 alleles (36%), followed by t he 1448C (444(Leu-->Pro)) mutation, that was found in 12 alleles (24%) . A complete gene deletion was present in two alleles (4%). The IVS1+2 (splicing mutation), the 1504T (463(Arg-->Cys)) as well as the 1342C (409(Asp-->His)) mutations were each present in one allele (2%). None of the alleles carried the 84GG (frameshift), 1604A (496(Arg-->His)) o r the 1297T (394(Val-->Leu)) mutation. This distribution is different from the Ashkenazi Jewish population but is similar to other Caucasian groups like the Spanish and Portuguese populations. Our results confi rm the variability of mutation patterns in Gaucher patients of differe nt ethnic origin. All patients were divided into nine groups according to their genotype and their clinical status was related to the indivi dual genotype. Genotype/phenotype characteristics of the 1226G, 1448C, and 1342C mutations of previous studies were confirmed by our results .