LAMP Human NUDT15 Deficiency KIT

Regulatory Status: CE-IVD

Format: 24 reactions 

Target gene: NUDT15 (NUDIX hydrolase 15)

Drug relevance: Thiopurines - azathioprine, 6-mercaptopurine, 6-thioguanine (reduced NUDT15 activity → thiopurine hpersensitivity / severe toxicity). Complementary to TPMT. 

Variants detected: NUDT15*3 (rs116855232), *6 (rs746071566, c.55_56insGAGTCG), *9 (rs746071566, c.50delGAGTCG)

Method: LAMP + meting curve analysis 

Sample: EDTA whole blood - no DNA extraction required - or extracted DNA

Compatible instruments: LightCycler 480 I&II / Cobas z 480 (Roche); CFX96 / CFX Opus 96 (Bio-Rad); QuantStudio 1/3/5 & 6/7 Flex (Applied Biosystems); MIC qPCR (Bio Molecular Systems); LC-Genie III & Genie HT (Optigene)

Software / result interpretation: Automated genotype calling via GeneFox software; mandatory visual confirmation of the melting curve

Turn around time: < 1h 

NUDIX hydrolase 15 (NUDT15) is an enzyme directly involved in the metabolism of thiopurines, a class of immunosuppressive drugs, as it catalyzes the conversion of active metabolites into less toxic metabolites. Thiopurines are the mainstay in the treatment of several forms of cancer, immune system disorders and the prevention of rejection after organ transplantation. Individuals with reduced or absent NUDT15 activity have a higher sensitivity to thiopurines at standard doses and are at a higher risk of toxic side effects.

Genetic variations in the TPMT and NUDT15 genes strongly influence the safety of thiopurine therapy. The genotyping of NUDT15 is therefore complementary to the identification of the TPMT risk allele: the latter is the main genetic cause of thiopurine intolerance in Europeans and Africans, while NUDT15 deficiency is most common among in Asians.