Gaucher disease associated with a unique KpnI restriction site: identification of the amino-acid substitution.

In an earlier survey of the glucocerebrosidase locus using 20 restriction enzymes and a 1039 bp probe we found that 1 of 9 Gaucher disease patients had a unique pattern with KpnI. a pattern that was not observed in any other Gaucher patient or in 31 controls. We have now localized the mutation in this patient to a T----A transversion in nucleotide 764 of the cDNA occurring on one of the two glucocerebrosidase alleles. The presumed abnormality in the other allele has not been identified. The deduced amino-acid change in the allele with the mutation at nucleotide 764 is a relatively drastic alteration of amino acid 255 from phenylalanine to tyrosine. The genomic DNAs of 31 other Gaucher disease patients (representing 62 Gaucher disease alleles) were examined for this mutation using the polymerase chain reaction. None were found to have this abnormality.