Novel thiopurine S-methyltransferase (TPMT) variant identified in Malay individuals

What is it about?

Thiopurine S-methyltransferase (TPMT) polymorphism can affect metabolism of thiopurine drugs and pharmacogenetic testing of this gene play a crucial role in dose optimization and minimizing adverse reactions. Here, we report the identification of a novel TPMT variant, NC_000006.12(NM_000367.5):c.142_146delinsAA, in a 28-year-old Malay male using capillary electrophoresis sequencing of the TPMT messenger RNA. This variant, located in exon 3 of the TPMT gene, induces an in-frame deletion-insertion, resulting in the removal of two leucine residues and the insertion of a lysine residue in the TPMT protein. Through high-throughput sequencing of the messenger RNA and genomic DNA, we validated the presence of this variant and its heterozygous presentation. Despite its absence in major genomic databases, the variant was detected in three other unrelated Malay patients in our internal database, suggesting potential specificity to the Malay population. The observed reduction in TPMT enzyme activity raises concerns regarding thiopurine drug metabolism and toxicity. Furthermore, the classification of the variant as a variant of uncertain significance highlights the need for further investigation into its clinical implications for personalized medicine.

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