Identification and characterization of a novel mutation c.1090G>T (G325W) and nine common mutant alleles leading to Gaucher disease in Spanish patients.

摘要: Abstract ABSTRACT Background. Gaucher disease is an autosomal recessive disorder resulting from mutations in the glucocerebrosidase gene (GBA). The lack of full genotype/phenotype correlation complicates counseling regarding clinical outcome and treatment recommendations. Subjects methods. Several human β-glucosidase associated with 16 Spanish families were identified utilizing a combination methods: enzymatic restriction, PCR–SSCP, sequence analyses. Expression studies performed following introduction mutagenized acid cDNA into COS-1 cells, residual enzyme activities mutant protein measured compared normal cDNA. Results. corresponding expressed are as follows: c.517A>C (T134P), 1%; c.721G>A (G202R), 17%; c.1090G>T (G325W), 13.9%; c.1093G>A (E326K), 26%; c.1208G>A (S364N), 4.1%; c.1226A>G (N370S), 17,8%; c.1246G>A (G377S), 17.6%; c.1289C>T (P391L), 8.5%; c.1448T>C (L444P), 3%; c.1504C>T (R463C), 24.5%. Conclusions. Site-directed mutagenesis expression cells useful methods to increase our understanding causality between severity, defects, activity. Our study demonstrates functional consequences (T134P, S364N, G377S, P391L, G325W) provide evidence for molecular biochemical basis disease, among patients ancestry.