Gene rearranagement on 1q21 introducing a duplication of the glucocerebrosidase pseudogene and a metaxin fusion gene.

The genes for glucocerebrosidase and metaxin, both located on chromosome 1q21, each have a highly homologous pseudogene sequence nearby. We describe a novel recombinant allele consisting of a duplication of the glucocerebrosidase pseudogene and a fusion between the metaxin gene and its pseudogene, resulting from a crossover between metaxin and pseudometaxin in the region downstream of the glucocerebrosidase gene. We also show that certain individuals have a metaxin-pseudometaxin fusion gene without a duplication, resulting from the same crossover. DNA from patients with Gaucher disease and normal controls were screened for recombinant alleles by Southern blot analyses prepared with the restriction enzymes SspI and HincII and by direct sequencing. Downstream alterations were identified in eight of the 398 patient alleles studied and in seven of the 200 normal control alleles examined, and were encountered more frequently among patients and controls of African-American ancestry. This is the first recognition of a duplicated allele in the glucocerebrosidase gene region, and its presence may contribute to genotype-phenotype studies in Gaucher disease.