Back-to-Back Comparison of Third-Generation Sequencing and Next-Generation Sequencing in Carrier Screening of Thalassemia

作者：Renliang Huang, Yinyin Liu, Jing Xu, Dan Lin, Aiping Mao, Liuqing Yang, Gaobu Zhong, Huoniao Wang, Ruofan Xu, Yi‐Wei Chen, Qiaomiao Zhou · 发表于：Archives of Pathology & Laboratory Medicine · 年份：2023 · DOI：10.5858/arpa.2022-0168-oa · 被引用次数：25 · 研究领域：Hemoglobinopathies and Related Disorders、Genomics and Rare Diseases、Blood groups and transfusion

CONTEXT.—: Recently, new technologies, such as next-generation sequencing and third-generation sequencing, have been used in carrier screening of thalassemia. However, there is no direct comparison between the 2 methods in carrier screening of thalassemia. OBJECTIVE.—: To compare the clinical performance of third-generation sequencing with next-generation sequencing in carrier screening of thalassemia. DESIGN.—: Next-generation sequencing and third-generation sequencing were simultaneously conducted for 1122 individuals in Hainan Province. RESULTS.—: Among 1122 genetic results, 1105 (98.48%) were concordant and 17 (1.52%) were discordant between the 2 methods. Among the 17 discordant results, 4 were common thalassemia variants, 9 were rare thalassemia variants, and 4 were variations with unknown pathogenicity. Sanger sequencing and polymerase chain reaction for discordant samples confirmed all the results of third-generation sequencing. Among the 685 individuals with common and rare thalassemia variants detected by third-generation sequencing, 512 (74.74%) were carriers of α-thalassemia, 110 (16.06%) were carriers of β-thalassemia, and 63 (9.20%) had coinheritance of α-thalassemia and β-thalassemia. Three thalassemia variants were reported for the first time in Hainan Province, including -THAI, -α2.4, and ααααanti3.7. Eleven variants with potential pathogenicity were identified in 36 patients with positive hemoglobin test results. Among 52 individuals with negative hemoglobin...