Detection of maternal carriers of common α-thalassemia deletions from cell-free DNA

• Published in: Scientific reports Vol. 12; no. 1; pp. 13581 - 9
• Main Authors: Doan, Phuoc-Loc, Nguyen, Duy-Anh, Le, Quang Thanh, Hoang, Diem-Tuyet Thi, Nguyen, Huu Du, Nguyen, Canh Chuong, Doan, Kim Phuong Thi, Tran, Nhat Thang, Ha, Thi Minh Thi, Trinh, Thu Huong Nhat, Nguyen, Van Thong, Bui, Chi Thuong, Lai, Ngoc-Diep Thi, Duong, Thanh Hien, Mai, Hai-Ly, Huynh, Pham-Uyen Vinh, Huynh, Thu Thanh Thi, Le, Quang Vinh, Vo, Thanh Binh, Dao, Thi Hong-Thuy, Vo, Phuong Anh, Le, Duy-Khang Nguyen, Tran, Ngoc Nhu Thi, Tran, Quynh Nhu Thi, Van, Yen-Linh Thi, Tran, Huyen-Trang Thi, Nguyen, Hoai Thi, Nguyen, Phuong-Uyen, Do, Thanh-Thuy Thi, Truong, Dinh-Kiet, Tang, Hung Sang, Cao, Ngoc-Phuong Thi, Lam, Tuan-Thanh, Tran, Le Son, Nguyen, Hoai-Nghia, Giang, Hoa, Phan, Minh-Duy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/208; 631/61; 692/699; alpha-Globins - genetics; alpha-Thalassemia - diagnosis; alpha-Thalassemia - genetics; beta-Thalassemia - genetics; Blood diseases; Cell-Free Nucleic Acids; China; Female; Fetuses; Genotype; Genotypes; Humanities and Social Sciences; Humans; multidisciplinary; Mutation; Polymerase Chain Reaction - methods; Pregnancy; Science; Science (multidisciplinary); Thalassemia; China
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-17718-7

α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/−− SEA (4.066%), αα/−α 3.7 (2.934%), αα/−α 4.2 (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14–99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (−α 3.7 /−α 4.2 , αα/−− THAI , −α 3.7 /−− SEA , −α 4.2 /−− SEA ). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−− SEA , 94.87% for αα/−α 3.7 , and 96.51% for αα/−α 4.2 ; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.