Scientific Reports (Aug 2022)

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

  • Phuoc-Loc Doan,
  • Duy-Anh Nguyen,
  • Quang Thanh Le,
  • Diem-Tuyet Thi Hoang,
  • Huu Du Nguyen,
  • Canh Chuong Nguyen,
  • Kim Phuong Thi Doan,
  • Nhat Thang Tran,
  • Thi Minh Thi Ha,
  • Thu Huong Nhat Trinh,
  • Van Thong Nguyen,
  • Chi Thuong Bui,
  • Ngoc-Diep Thi Lai,
  • Thanh Hien Duong,
  • Hai-Ly Mai,
  • Pham-Uyen Vinh Huynh,
  • Thu Thanh Thi Huynh,
  • Quang Vinh Le,
  • Thanh Binh Vo,
  • Thi Hong-Thuy Dao,
  • Phuong Anh Vo,
  • Duy-Khang Nguyen Le,
  • Ngoc Nhu Thi Tran,
  • Quynh Nhu Thi Tran,
  • Yen-Linh Thi Van,
  • Huyen-Trang Thi Tran,
  • Hoai Thi Nguyen,
  • Phuong-Uyen Nguyen,
  • Thanh-Thuy Thi Do,
  • Dinh-Kiet Truong,
  • Hung Sang Tang,
  • Ngoc-Phuong Thi Cao,
  • Tuan-Thanh Lam,
  • Le Son Tran,
  • Hoai-Nghia Nguyen,
  • Hoa Giang,
  • Minh-Duy Phan

DOI
https://doi.org/10.1038/s41598-022-17718-7
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 9

Abstract

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Abstract 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/−α3.7 (2.934%), αα/−α4.2 (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 (−α3.7/−α4.2, αα/−−THAI, −α3.7/−−SEA, −α4.2/−−SEA). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−−SEA, 94.87% for αα/−α3.7, and 96.51% for αα/−α4.2; 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.