Identification of two novel mutant alleles of human thiopurine S-methyltransferase, and diagnostic uses thereof

摘要

Mutants of thiopurine S-methyltransferase (TPMT) are described. TPMTA mutant has a point mutation at cDNA position 238 (G238->C), and TPMTB involves two nucleotide transitions at cDNA positions 460 (G460->A) and 719 (A719->G). TPMTB is the predominant mutant allele associated with human TPMT-deficiency which can cause potentially fatal toxicity when patients are treated with mercaptopurine, azathioprine, or thioguanine. The mutant alleles as well as PCR fragments, mutant proteins and antibodies therefor, together with kits and methods for assaying the TPMT genotype of individual patients are disclosed.