Seven members of an Ashkenazi Jewish family with Gaucher disease in 3 successive 
generations were tested for the presence of the 2 common mutations known to 
occur in the glucocerebrosidase gene. Genomic DNA from blood or skin fibroblasts 
of relatives was amplified by using the PCR technique and individual mutations 
identified by oligonucleotides specific to the mutated sequences. Four 
individuals were homozygous for a mutation at amino acid 370 (370 mutation) 
known to occur only in type 1 disease. The other 3 affected relatives were 
compound heterozygotes for this mutation and for a mutation at amino acid 444 
(NciI mutation) which, in the homozygous state, is associated with neurological 
disease. Clinical severity was more marked in the compound heterozygotes than in 
the homozygotes. Since the mutation is present in Ashkenazim, molecular 
diagnosis in families which carry the NciI mutation should prove useful in 
assessing their risk of the neurologic forms of Gaucher disease.