title: Gaucher disease: four families with previously undescribed mutations.
abstract: We describe four families with patients with type I Gaucher disease exhibiting previously undescribed mutations of the glucocerebrosidase gene. We found Cherokee Indian woman to have a G-->C substitution in cDNA nucleotide 354, predicting a lysine-->aspargine substitution in amino acid 79 of the processed protein. In a Greek family, we found an allele with a C-->T substitution in nucleotide 475 giving rise to an arginine-->tryptophan substitution at amino acid 120. In another non-Jewish European patient, we identified a C-->T substitution in nucleotide 1223, predicting a threonine-->methionine mutation in amino acid 369. We found two non-Jewish European children to have a C-->T mutation at nucleotide 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 manifestations. Finding the reason for these differences is an important goal in the study of Gaucher disease.
authors.affiliation: Scripps Research Institute, Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, CA 92037, USA.
authors.forename: E
authors.initials: E
authors.lastname: Beutler
authors.forename: T
authors.initials: T
authors.lastname: Gelbart
authors.forename: D
authors.initials: D
authors.lastname: Balicki
authors.forename: A
authors.initials: A
authors.lastname: Demina
authors.forename: J
authors.initials: J
authors.lastname: Adusumalli
authors.forename: L
authors.initials: L
authors.lastname: Elsas
authors.forename: K A
authors.initials: KA
authors.lastname: Grinzaid
authors.forename: R
authors.initials: R
authors.lastname: Gitzelmann
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: C
authors.initials: C
authors.lastname: Kattamis
authors.forename: B B
authors.initials: BB
authors.lastname: Liou
mesh_terms: D000328:Adult; D002648:Child; D005190:Family; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation
chemical_list: D005962:Glucosylceramidase