Abstract
Aim: To assess rare TPMT variants in patients carrying a deficient phenotype not predicted by the fourmore frequent genotypes (*2, *3A, *3B and *3C). Materials & methods: Next-generation sequencing of TPMT in 39 patients with a discordant genotype. Results: None of the variants identified explained the discordances assuming that they are of uncertain significance according to the Clinical Pharmacogenetics Implementation Consortium classification.Two unknown variants were detected and predicted to result in a splicing defect. We show that TPMT*16and TMPT*21 are defective alleles, and TPMT*8 and TPMT*24 are associated with a normal activity. Conclusion: Whole-exon sequencing for rareTPMT mutations has a low diagnostic yield. A reassessment of the functional impact of rare variants of uncertain significance is a critical issue.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
