GAUCHER-DISEASE - 4 FAMILIES WITH PREVIOUSLY UNDESCRIBED MUTATIONS

We describe four families with patients with type I Gaucher disease ex hibiting previously undescribed mutations of the glucocerebrosidase ge ne. We found Cherokee Indian woman to have a G-->C substitution in cDN A nucleotide 354, predicting a lysine-->aspargine substitution in amin o acid 79 of the processed protein. In a Greek family, we found an all ele with a C-->T substitution in nucleotide 475 giving rise to an argi nine-->tryptophan substitution at amino acid 120. In another non-Jewis h European patient, we identified a C-->T substitution in nucleotide 1 223, predicting a threonine-->methionine mutation in amino acid 369. W e found two non-Jewish European children to have a C-->T mutation at n ucleotide 1357, predicting termination at codon 414. Although siblings carry the same two glucocerebrosidase mutations, in these families as in others we noted considerable differences in severity of clinical m anifestations. Finding the reason for these differences is an importan t goal in the study of Gaucher disease.