Application of an optimized non-invasive prenatal testing for thalassemia based on change of haplotype doses

Fei Sun; Yao Zhou; Xing Zhao; Qiuling Jie; Linna Ma; Dan Lin; Yaxuan Li; Yangqing Mai; Ge Gao; Yongfang Zhang; Qi Li; Yanlin Ma

doi:10.1016/j.jgg.2025.09.007

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Application of an optimized non-invasive prenatal testing for thalassemia based on change of haplotype doses

doi: 10.1016/j.jgg.2025.09.007

Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education, Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Province, Hainan Provincial Clinical Research Center for Thalassemia, Department of Reproductive Medicine, The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan 571101, China

Funds:

This work was supported by the National Key R&D Program of China (2024YFA1802300), the Major Science and Technology Program of Hainan Province (ZDKJ2021037), the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China (U24A20677) and Hainan Province Science and Technology Special Fund (ZDYF2020117, ZDYF2022SHFZ312), Hainan Province Science and Technology Project (LCXY202102, LCYX202203, LCYX202301, LCYX202502) and Innovative research project for postgraduate students in Hainan Medical University (HYYB2021A05), project supported by Hainan Province Clinical Medical Center, the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202310). We thank all the investigators who participated in the present study and Basecare Medical Device Co., Ltd., Suzhou.

Received Date: 2025-06-13
Accepted Date: 2025-09-19
Rev Recd Date: 2025-09-17

Available Online: 2025-09-26

Abstract

Abstract

Patients affected by monogenic diseases impose a substantial burden on both themselves and their families. The primary preventive measure, i.e., invasive prenatal diagnosis, carries a risk of miscarriage and cannot be performed early in pregnancy. Hence, there is a need for non-invasive prenatal testing (NIPT) for monogenic diseases. By utilizing enriched cell-free fetal DNA (cffDNA) from maternal plasma, we refine the NIPT method, which combines targeted region capture technology, haplotyping, and analysis of informative site frequency. We apply this method to 93 clinical families at genetic risk for thalassemia, encompassing various genetic variant types, to establish a workflow and evaluate its efficiency. Our approach requires only 3 ng of DNA input to generate 0.1 GB of informative target genomic data and leverages a minimum of 3% cffDNA. This method has a 98.16% success rate and 100% concordance with conventional invasive methods. Furthermore, we demonstrate the ability to analyze fetal genotypes as early as eight weeks of gestation. This study establishes an optimized NIPT method for the early detection of various thalassemia disorders during pregnancy. This technique demonstrates high accuracy and potential for clinical application in prenatal diagnosis.
- Cell-free fetal DNA,
- Non-invasive prenatal testing,
- Thalassemia,
- Hybrid capture,
- Haplotype

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References(27)

References

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