Mutation analysis of an Ashkenazi Jewish family with Gaucher disease in three successive generations.

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.