Heterogeneity in type I Gaucher disease demonstrated by restriction mapping of the gene.

A cloned fragment of human glucocerebrosidase cDNA has been used as a probe to study restriction polymorphisms in the region of the gene for Gaucher disease. Variability in the size of fragments produced by digestion with the restriction endonucleases Pvu II and Kpn I was discovered. The Pvu II polymorphism was found to be a very prevalent one with a gene frequency of 0.65 for the Pv1.1- allele and 0.35 for the Pv1.1+ allele. Similar frequencies were encountered among diverse ethnic groups. Five of eight Jewish patients with Gaucher disease were found to be heterozygous for the Pvu II restriction polymorphism. One non-Jewish patient with type I Gaucher disease was heterozygous for the Kpn I variant. The existence of Gaucher disease genes in association with either allele of the ancient Pvu II polymorphism clearly indicates that, even within the Jewish population, the Gaucher disease mutation has occurred independently more than once. Presumably, different mutations have also occurred in the non-Jewish population.