LAUSR

BACKGROUND Thalassemia is one of most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous SEA deletion (--/--) in the HBA gene. Few studies has proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE In this study, we aim to develop a non-invasive method of target-captured sequencing and genotyping by Bayesian method using cff-DNA to identify the fetal genotype in pregnant women who are at risk of having Hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian (SEA) type (--/αα) of α-thalassemia. Prenatal diagnosis was performed by CVS, amniocentesis or cordocentesis using gap-PCR considered as the golden standard. RESULTS As a result, we can found that the sensitivity and specificity of our non-invasive method were 98.81% and 94.72%, respectively, in the training set, as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the SEA carrier and 36 trisomy samples with 100% of sensitivity in T13, T18 and T21 and, while 99.89% (1/917) and 99.88% (1/888) of specificity in T18 and T21, respectively. CONCLUSIONS Our method opens the possibility of early screening for maternal genotyping of α- thalassemia, fetal aneuploidies in chromosomes 13/18/21, and Hemoglobin Bart hydrops fetalis detection in one tube of maternal plasma.