title: Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing.
abstract: Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China; kang.zhang@gmail.com canliao@hotmail.com hlliu@igenomics.com.cn Zhangxiaozhuang55@126.com.
authors.forename: Can
authors.initials: C
authors.lastname: Liao
authors.affiliation: Prenatal Diagnosis Centre andMaternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 510010, China;Guangdong Thalassemia Diagnostic Centre, Guangzhou 510010, China;
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Yin
authors.affiliation: iGenomics Co., Ltd., Guangzhou 510005, China;
authors.forename: Chun-fang
authors.initials: CF
authors.lastname: Peng
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China;
authors.forename: Fang
authors.initials: F
authors.lastname: Fu
authors.affiliation: Prenatal Diagnosis Centre andMaternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 510010, China;
authors.forename: Jie-xia
authors.initials: JX
authors.lastname: Yang
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China;
authors.forename: Ru
authors.initials: R
authors.lastname: Li
authors.affiliation: iGenomics Co., Ltd., Guangzhou 510005, China;
authors.forename: Yang-yi
authors.initials: YY
authors.lastname: Chen
authors.affiliation: iGenomics Co., Ltd., Guangzhou 510005, China;
authors.forename: Dong-hong
authors.initials: DH
authors.lastname: Luo
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China;
authors.forename: Yong-ling
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China;
authors.forename: Yan-mei
authors.initials: YM
authors.lastname: Ou
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China;
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Prenatal Diagnosis Centre andMaternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 510010, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Prenatal Diagnosis Centre andMaternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 510010, China;
authors.forename: Ming-qin
authors.initials: MQ
authors.lastname: Mai
authors.affiliation: Guangzhou Kang Rui Biological Pharmaceutical Technology Co., Ltd., Guangzhou Development District, Guangzhou 510005, China;
authors.forename: Rui
authors.initials: R
authors.lastname: Hou
authors.affiliation: Institute for Genomic Medicine and Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92328;
authors.forename: Frances
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institute for Genomic Medicine and Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92328;Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital and Sichuan University, Chengdu 610041, China; and.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China;
authors.forename: Dong-zhi
authors.initials: DZ
authors.lastname: Li
authors.affiliation: iGenomics Co., Ltd., Guangzhou 510005, China; kang.zhang@gmail.com canliao@hotmail.com hlliu@igenomics.com.cn Zhangxiaozhuang55@126.com.
authors.forename: Hai-liang
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Prenatal Diagnosis Centre andMaternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 510010, China;Guangdong Thalassemia Diagnostic Centre, Guangzhou 510010, China; kang.zhang@gmail.com canliao@hotmail.com hlliu@igenomics.com.cn Zhangxiaozhuang55@126.com.
authors.forename: Xiao-zhuang
authors.initials: XZ
authors.lastname: Zhang
authors.affiliation: Institute for Genomic Medicine and Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92328;Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital and Sichuan University, Chengdu 610041, China; andVeterans Administration Healthcare System, San Diego, CA 92161 kang.zhang@gmail.com canliao@hotmail.com hlliu@igenomics.com.cn Zhangxiaozhuang55@126.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000782:Aneuploidy; D025063:Chromosome Disorders / Q000175:diagnosis; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D003362:Cost-Benefit Analysis; D004314:Down Syndrome / Q000175:diagnosis; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies; D012189:Retrospective Studies; D012666:Semiconductors; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome