THIẾT LẬP VÀ ĐÁNH GIÁ QUI TRÌNH SÀNG LỌC TRƯỚC SINH KHÔNG XÂM LẤN CHO HỘI CHỨNG MẤT ĐOẠN 22Q11.2

Abstract

Background: Non-Invasive Prenatal Testing (NIPT) for common fetal chromosomal abnormalities is increasingly being used worldwide. Many recent studies have shown that NIPT using next-generation sequencing (NGS) is able to detect fetal diseases caused by microdeletion. The continuous improvement of the NGS method in prenatal screening will significantly reduce the burden of congenital birth defects and improve the quality of the Vietnamese population. In this study, we develop a non-invasive prenatal procedure by NGS method to screen for microdeletions causing Di George syndrome, providing a more comprehensive screening than traditional NIPT. Objective: Establish and validate a non-invasive prenatal testing protocol for early detection of Di George syndrome by determining the sensitivity and specificity of the test. Method: A total of 134 blood samples from singleton pregnant women over 9 weeks of gestation were collected, including 17 samples with fetal microdeletion at 22q11.2, and 117 negative samples. Cell-free DNA were extracted from plasma samples, barcoded, and then analyzed by the Nextseq 2000 system. The sequencing data were then transformed to normal gene signals and deletion signals. A machine learning model were trained using 10 positive and 10 negative samples, and validated on a test dataset of 7 positive and 107 negative samples.  Results: In a total of 114 tested samples, our method detected all 7 true positive samples but also identified 4 false positive samples. Meanwhile, 103/107 samples had been determined as true negative. We therefore reported that the analytical sensitivity of our method is >99%, the  analytical specificity is 96.3%, the positive predictive value is > 63.6%, and the negative predictive value is >99%. Conclusion: We established a non-invasive prenatal testing protocol to screen for fetal microdeletion, specifically at 22q11.2 causing DiGeorge syndrome. This is an important step towards expanding the scope of current noninvasive prenatal testing to detect a wide spectrum of fetal diseases caused by microdeletion