Three Gaucher-Disease-Producing Mutations in a Patient with Gaucher Disease: Mechanism and Diagnostic Implications

As Gaucher disease is an autosomal recessive disorder, most patients are either homozygotes or compound heterozygotes for glucocerebrosidase mutations. We have encountered a patient with three mutations, two c.1226A -> G (1226G, N370S) and one c.1448 T-> C (1448C, L444P). This was shown to be due to a gene conversion event in which the sequence of the glucocerebrosidase pseudogene that includes the 1448C mutation had been imposed on a glucocerebrosidase gene that already had the 1226G mutation. The patient had relatively mild disease which had been discovered after an attack of infectious mononucleosis, a relationship that has been observed previously. If it had not been recognized that this patient had the 1226G/1226G,1448C genotype, prenatal testing might have falsely identified a 1226G,1448C/wt (wild type) fetus as having Gaucher disease.