Thalassemia screening by third-generation sequencing: Pilot study in a Thai population

Abstract

Background Conventional thalassemia screening takes a stepwise approach and has limitations in comprehensively identifying all spectrums of mutations. This study aimed to investigate the performance of third-generation sequencing (TGS) compared to conventional molecular testing. Methods TGS was applied to validate all known variants detected by conventional testing and to detect missing variants in undiagnosed cases. The study was conducted at Maharaj Nakorn Chiang Mai Hospital between December 2021 and April 2022. Results In total, 19 cases were included in this study, among which 52.6% (10/19) had known thalassemia variants, while 47.7% (9/19) cases were undiagnosed by conventional methods. All 16 variants previously detected were validated by TGS, and TGS additionally detected 43.8% (7/16) thalassemia variants for 36.8% (7/19) cases. Conclusion TGS could provide additional genetic diagnoses compared with conventional methods. Further cost-effectiveness studies with a larger sample size are needed to explore the role of TGS in clinical practices.