TRANSFER BY BMT OF IGG2 DEFICIENCY INVOLVING AN IMMUNOGLOBULIN HEAVY-CHAIN CONSTANT REGION DELETION AND A SILENT IGG2 GENE

A patient suffering from ALL who underwent allogeneic BMT developed co mplete IgG2 deficiency after BMT. When the donor Ig serum levels were examined, it was found that he also lacked deteCtable leveLs of IgG2. The IGHC genes were investigated and a heterozygous 50-70 kb deletion encompassing the genes coding for IgG2 (G2) and IgG4 (G4) (del G2-G4) was found in the white blood cells. The patient had IgG2 levels in the low normal range before BMT. When the patient's fibroblasts were exam ined to determine his original genotype, they were found to carry the same deletion haplotype, but in combination with a different G2 allele than that present in the transplanted BM cells. The combination of Ig heavy chain constant region gene alleles found in the transplant had also been inherited by a third brother also lacking IgG2. The hemizygo us G2 allele present in the donated BM cells was thus 'silent' and the complete IgG2 deficiency had been transferred by the BMT.