Molecular Diagnosis of Thiopurine S-Methyltransferase Deficiency
Authors: Eugene Y. Krynetski
Journal: Annals of Internal Medicine (1997)

Letters1 December 1997Molecular Diagnosis of Thiopurine S-Methyltransferase DeficiencyEugene Y. Krynetski, PhD and William E. Evans, PharmDEugene Y. Krynetski, PhDSt. Jude Children's Research Hospital; Memphis, TN 38101Search for more papers by this author and William E. Evans, PharmDSt. Jude Children's Research Hospital; Memphis, TN 38101Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-11-199712010-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We are pleased by Dr. Blank's interest in our paper and offer the following in response to points raised in his letter. We have previously shown that the G238C transversion alone is associated with a 100-fold reduction in TPM catalytic activity in a heterologous expression system [1] and that this is the only mutation in some patients with TPM deficiency [1]. Likewise, we have shown that the G460A and the A719G mutations are the only mutations in the TPM complementary DNA (cDNA) of other patients with TPM deficiency, and that the cDNA with only these mutations has more ...References1. Krynetski EY, Schuetz JD, Galpin AJ, Pui CH, Relling MV, Evans WE. A single point mutation leading to loss of catalytic activity in human hiopurine S-methyltransferase. Proc Natl Acad Sci U S A. 1995; 92:949-53. Google Scholar2. Tai HL, Krynetski EY, Yates CR, Loennechen T, Fessing MY, Krynetskaia NF, et al. Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in caucasians. Am J Hum Genet. 1996; 58:694-702. Google Scholar3. Szumlanski C, Otterness D, Her C, Lee D, Brandiff B, Kelsell D, et al. Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. DNA Cell Biol. 1996; 15:17-30. Google Scholar4. Tai HL, Krynetski EY, Schuetz EG, Yanishevski Y, Evans WE. Enhanced proteolysis of thiopurine S-methyltransferase (TPM) encoded by mutant alleles in humans (TPM*3A, TPM*2): mechanisms for the genetic polymorphism of TPM activity. Proc Natl Acad Sci U S A. 1997; 94:6444-9. Google Scholar5. Krynetski EY, Tai HL, Yates CR, Fessing M, Loennechen T, Schuetz JD, et al. Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms. Pharmacogenetics. 1996; 6:279-90. Google Scholar Author, Article, and Disclosure InformationAuthors: Eugene Y. Krynetski, PhD; William E. Evans, PharmDAffiliations: St. Jude Children's Research Hospital; Memphis, TN 38101 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1997Volume 127, Issue 11Page: 1041-1042KeywordsAllelesComplementary DNAGenetic polymorphismGenotypingHeterozygosityPhenotypesProteinsProteolysis ePublished: 15 August 2000 Issue Published: 1 December 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...