A rare G6490→A substitution at the last nucleotide of exon 10 of the glucocerebrosidase gene in two unrelated Italian Gaucher patients

Mutation screening of the glucocerebrosidase gene by SSCP analysis revealed an abnormal pattern of exon 10 in two unrelated Italian Gaucher patients. Direct sequencing of the mutated samples identified a G6490 A transition. The same mutation has been described before in a Japanese patient with Gaucher disease type III. The clinical phenotype of our patients was type I in one whose second allele carried the N370S mutation and type II in the other one with a L444P mutation. In this latter the G6490 A substitution cancels a normal Msp I site, while on the opposite chromosome the T6433 C mutation (L444P) introduces a new Msp I site. Thus, digestion with Msp I of the amplified exon 10 is a useful method for identifying the two mutations simultaneously.