Mutation analysis of Gaucher disease patients from Argentina: High prevalence of the RecNciI mutation

Gaucher disease (GD) is caused by a deficiency of beta-glucocerebrosidase a ctivity mainly due to mutations in the gene coding for the enzyme, More tha n 100 mutations have been identified to date and their frequencies have bee n established in several populations, including Ashkenazi Jews, among whom the disease is particularly prevalent. In order to study the molecular path ology of the disease in patients from Argentina, we conducted a systematic search for mutations in the glucocerebrosidase gene. Genomic DNA from 31 un related GD patients was screened for seven previously described mutations: N370S (1226A-->G), L444P (1448T-->C), D409H (1342G-->C), R463C (1504C-->T), 1263del55, RecNciI, and RecTL. This allowed the identification of 77.4% of the GD alleles: N370S and RecNciI were the most prevalent mutations found (46.8% and 21% respectively). Southern analysis demonstrated three distinct patterns for the RecNciI alleles, In order to identify the remaining allel es, the full coding region of the gene, all the splice sites, and part of t he promoter region were analyzed by single-strand conformational polymorphi sm analysis (SSCP) after polymerase chain reaction amplification. This exte nsive screening allowed the identification of 13 different mutations, accou nting for 93% of the total number of GD alleles, Three novel missense mutat ions, I161S (599T-->G), G265D (911G-->A), and F411I (1348T-->A), were detec ted. Twelve polymorphic sites within the glucocerebrosidase gene are in com plete linkage disequilibrium and define two major haplotypes, "-" and "+". Mutation N370S was always associated with the "-" haplotype, as described i n other populations. Interestingly, the RecNciI alleles with the same South ern-blot pattern were always associated with the same haplotype, Am. J. Med . Genet. 80:343-351, 1998. (C) 1998 Wiley-Liss, Inc.