Differences in origin of the 1448C mutation in patients with Gaucher disease

Gaucher disease (GD) can be caused by any of over 50 mutations of the gene of glucocerebrosidase (D-glucosyl acylsphingosine glucohydrolase; EC 3.2.1.45). The 1448T to C mutation is found among all ethnic groups. In Ashkenazi Jews, the patients who are homozygous for the 1448C mutation are associated with the neuropathic form of the disease, but this is not the case in Japanese patients. This present study was the analysis of the two haplotypes, the Pv1.1 and the liver/erythrocytes pyruvate kinase (PKLR), in Japanese GD patients who were homo- or heterozygous for the 1448C mutation, and comparison of the results with other ethnic patients with the same genotypes in order to show ethnic differences. Of 28 patients, 20 had type I disease (7 were homozygous for the 1448C), five had type II (1 was homozygous) and 3 had type III (all were heterozygous). In Japanese GD patients with the 1448C mutation, the two haplotypes showed complete matching in (+) or (-). The Pv1.1/PKLR(+) alleles accounted for 84.0% and this frequency was opposite to that reported in Ashkenazi Jews and other Caucasians. The 1448C homozygous state showed no obvious linkage with either of the haplotypes. From this haplotype analysis, it is postulated that the origin of the 1448C mutation in Japanese GD patients is different from that reported in other ethnic groups.