[Expert consensus on the clinical application of Single-Molecule Real-Time Sequencing in the precise prevention and control of Thalassemia (2025 Edition)].

Thalassemia is a highly prevalent genetic hemoglobinopathy, with approximately 350 million people worldwide carrying variants of the globin genes. The carrier rate in southern China is as high as 10% ~ 25%. The "multi-level sequential screening and diagnosis" approach, which uses hematological screening, hotspot mutation testing, and genetic testing based on other technologies to diagnose rare types of thalassemia, has proven to be highly effective for the prevention and control of thalassemia. However, its cumbersome process, high cost for testing and medical labor, and high demand for genetic consulting have obvious limitations. For its advantages of long reads and accurate identification of sequence variants, Single-Molecule Real-Time (SMRT) Sequencing technology can not only broaden the scope of globin gene mutation detection, but also directly distinguish the haplotypes and structural rearrangements of the α- and β-globin genes, significantly improving the detection rate, reducing false positives and missed detection, and has revolutionized the detection for genetic variants underlying thalassemia. With the maturity of technology and decrease in cost, the application of SMRT sequencing in the prevention and control of thalassemia is becoming increasingly widespread. So far more than 50 clinical studies and 300,000 clinical application data have been accumulated. Based on these evidence-based studies, this consensus has explored the application scope, workflow, and limitations of employing SMRT sequencing in clinical genetic testing for thalassemia. It aims to provide recommendations and guidance for clinicians, laboratory staff, and policy makers, to support precise prevention and control of thalassemia throughout the full life cycle.