title: Noninvasive Prenatal Screening of Fetal Aneuploidy without Massively Parallel Sequencing.
abstract: Noninvasive prenatal screening (NIPS) using plasma cell-free DNA has gained tremendous popularity in the clinical assessment of fetal aneuploidy. Most, if not all, of these tests rely on complex and expensive massively parallel sequencing (MPS) techniques, hindering the use of NIPS as a common screening procedure.
  
  
  
  We have developed and optimized an MPS-independent noninvasive genetic test that can rapidly detect fetal aneuploidy at considerably lower costs. We used the high-throughput ligation-dependent probe amplification (HLPA) assay with standardzscore statistics to identify the minute copy number change of targeted chromosomal regions. HLPA was modified from multiplex ligation-dependent probe amplification to allow quantification of up to 200 genomic loci in a single multiplex PCR. As a proof of principle, we conducted Down syndrome screening in 1182 women with singleton pregnancies [maternal age (SD): 32.7 (4.6)] using whole-genome sequencing-based NIPS and our method.
  
  
  
  Nineteen fetuses with trisomy 21 were detected by both methods and confirmed by karyotyping of amniotic fluid. Overall, our method showed 100.0% sensitivity (19/19) and 99.7% specificity (1076/1079) in trisomy 21 screening, generating a positive predictive value of 86.4% (19/22) and a 7.1% (84/1182) no-call rate.
  
  
  
  Our technique potentially opens new avenues for the development of inexpensive, yet effective, prenatal aneuploidy tests. The simplicity and accuracy of this method make it a good candidate for clinical implementation as a standard screening procedure.
authors.affiliation: Institute of Embryo-Fetal Original Adult Disease affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.|International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chenming
authors.initials: C
authors.lastname: Xu
authors.affiliation: Suzhou Municipal Hospital affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Suzhou Municipal Hospital affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Embryo-Fetal Original Adult Disease affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.|International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Songchang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Huang
authors.affiliation: Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China. zhengwenj@geneskies.com.
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000782:Aneuploidy; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009030:Mosaicism; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D014314:Trisomy / Q000235:genetics*
chemical_list: D004247:DNA