A Prospective Multi-Center Newborn Screening for Thalassemia by Comprehensive Analysis of Thalassemia Alleles (CATSA) Based on Single Molecule Real-Time Sequencing in Guangxi, China.

Thalassemia is one of the most common inherited diseases in Guangxi, China. Early identification of thalassemia by neonatal screening is beneficial for effective clinical management and treatment. A total of 3671 newborns from multiple centers of Guangxi were prospectively recruited and screened for thalassemia using single molecule real-time (SMRT) sequencing technology. A total of 36 types of variants of globin genes were identified, including 16 common variants and 20 rare variants in the Chinese population. In total, 956 (26.04%) newborns were identified to carry thalassemia variants, including 672 (18.31%) α-thalassemia, 228 (6.21%) β-thalassemia, 55 (1.50%) combined α/β-thalassemia and 1 (0.03%) δ-thalassemia. In addition, this study showed that the carrier rates of structural variants of α-globin genes and abnormal hemoglobin variants were 1.28% and 0.93% respectively. Phenotypically, 12 newborns with hemoglobin H disease and 2 cases with intermedia β-thalassemia were found, two of whom would be misdiagnosed by conventional genetic analysis methods. Collectively, this study characterized the complexity and diversity of thalassemia gene variants in newborns of Guangxi, and further achieved early identification of newborns with intermedia thalassemia, which facilitated precision prevention of thalassemia in this region. Also, SMRT provided a powerful tool for neonatal thalassemia screening, especially in prevalent regions.