Xiaoqing Ye1, Shengmou Lin2, Xiwei Song3, Meihua Tan3, Jia Li3, Jiayan Wang1, Huanchen Yan1, Huimin Zhang4, Shaoying Li4, Dunjin Chen1, Min Chen5. 1. Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes, China. 2. Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Obstetrics and Gynaecology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. 3. BGI Genomics Co., Ltd, Shenzhen, 518083, China. 4. Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes, China. 5. Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes, China. Electronic address: edchen99@gmail.com.
Abstract
OBJECTIVE: To explore the clinical utility of detecting chromosome copy number variants (CNVs) in the fetus by noninvasive prenatal testing (NIPT) using the low-pass whole-genome sequencing. METHODS: Eight hundred and seventy-three singleton pregnancies with chromosomal microarray analysis (CMA) available between January 2017 to December 2019 and stored enough plasma sample for NIPT testing were included in this study. The CMA results show that forty-eight pregnancies with CNVs and eight hundred and twenty-five pregnancies are normal. Each pregnancy's plasma sample was blindly tested with NIPT at a depth of 0.51-1.19x for CNVs detection. The performance of the NIPT method for CNVs detection compared with the CMA method is evaluated. RESULTS: A total of fifty-two CNVs ranging from 0.1-47.3 Mb identified in forty-eight samples were identified by NIPT, of which thirty-four CNVs were consistent with CMA results. Additionally, eighteen CNVs were missed by NIPT. The overall sensitivity and specificity for the detection of CNVs were 65.38% (95% CI: 51.76%-76.89%) and 97.45% (95% CI: 96.12%-98.35%), respectively. However, for the detection of CNVs larger than 2 Mb and CNVs less than 2Mb, the sensitivities were 81.58% (95% CI: 66.27%-91.09%) and 21.43% (95% CI: 6.84%-48.32%), respectively. CONCLUSION: Our study demonstrated that the NIPT might be an alternative method for screening CNVs comparable with other studies. However, CNVs less than 2Mb in length shows poor sensitivity by NIPT. Noninvasive CNVs detection based on the NIPT method still needs more clinical validation studies and technical improvement to achieve clinically acceptable accuracy.
OBJECTIVE: To explore the clinical utility of detecting chromosome copy number variants (CNVs) in the fetus by noninvasive prenatal testing (NIPT) using the low-pass whole-genome sequencing. METHODS: Eight hundred and seventy-three singleton pregnancies with chromosomal microarray analysis (CMA) available between January 2017 to December 2019 and stored enough plasma sample for NIPT testing were included in this study. The CMA results show that forty-eight pregnancies with CNVs and eight hundred and twenty-five pregnancies are normal. Each pregnancy's plasma sample was blindly tested with NIPT at a depth of 0.51-1.19x for CNVs detection. The performance of the NIPT method for CNVs detection compared with the CMA method is evaluated. RESULTS: A total of fifty-two CNVs ranging from 0.1-47.3 Mb identified in forty-eight samples were identified by NIPT, of which thirty-four CNVs were consistent with CMA results. Additionally, eighteen CNVs were missed by NIPT. The overall sensitivity and specificity for the detection of CNVs were 65.38% (95% CI: 51.76%-76.89%) and 97.45% (95% CI: 96.12%-98.35%), respectively. However, for the detection of CNVs larger than 2 Mb and CNVs less than 2Mb, the sensitivities were 81.58% (95% CI: 66.27%-91.09%) and 21.43% (95% CI: 6.84%-48.32%), respectively. CONCLUSION: Our study demonstrated that the NIPT might be an alternative method for screening CNVs comparable with other studies. However, CNVs less than 2Mb in length shows poor sensitivity by NIPT. Noninvasive CNVs detection based on the NIPT method still needs more clinical validation studies and technical improvement to achieve clinically acceptable accuracy.