Polymorphisms in glucosylceramide (glucocerebroside) synthase and the Gaucher disease phenotype.
BACKGROUND
Gaucher disease results from the accumulation of glucosylceramide (glucocerebroside) in tissues of affected persons. Patients sharing the same genotype present with widely varying degrees of lipid storage and of clinical manifestations.


OBJECTIVE
To determine whether variation in the glucosylceramide synthase (UDPGlucose ceramide glucosyltransferase) gene, which encodes the enzyme that regulates the synthesis of glucocerebroside, could account for the variability and clinical manifestations.


METHODS
Patients homozygous for the 1226G (N370S) mutation, the most common in the Ashkenazi Jewish population, were investigated. The exons and flanking sequences of the gene were sequenced using DNA derived from five very mild Gaucher disease patients and four patients with relatively severe Gaucher disease.


RESULTS
One polymorphism was found in the coding region, but this did not change any amino acids. Seven other polymorphisms were found in introns and in the 5' untranslated region. Some of these were single nucleotide polymorphisms; others were insertions. The mutations appear to be in linkage equilibrium and none were found with a significantly higher frequency in either severe or mildly affected individuals.


CONCLUSIONS
Mutations in the glucosylceramide synthase gene do not appear to account for the variability in expression of the common Jewish Gaucher disease mutation.
Beutler
Ernest
E
Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, CA, USA. beutler@scripps.edu
West
Carol
C
D005776:Gaucher Disease / Q000145:classification / Q000235:genetics*; D005964:Glucosyltransferases / Q000235:genetics*; D006801:Humans; D007585:Jews; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase