Gene rearrangements in the glucocerebrosidase-metaxin region giving rise to disease-causing mutations and polymorphisms. Analysis of 25 Rec NciI alleles in Gaucher disease patients.

The glucocerebrosidase and metaxin genes lie in a gene-rich region that also includes two corresponding pseudogenes. This gives rise to recombinant alleles. We analysed two groups of patients from Argentina and Spain: 25 bearing the Rec NciI allele and 36 carrying L444P. The mutational mechanism is described and the crossover site precisely defined. Most of the Rec NciI alleles were generated by gene conversion. Rearranged alleles involving the metaxin gene were also identified. The high frequency of Rec NciI alleles associated with a polymorphic rearrangement at the metaxin level is probably due to a founder effect.