title: Copy number variation sequencing-based prenatal diagnosis using cell-free fetal DNA in amniotic fluid.
abstract: OBJECTIVE
  The study aimed to determine whether cell-free fetal DNA (cffDNA) present in amniotic fluid supernatant can be used as a surrogate for amniocyte-based diagnosis of fetal chromosomal abnormalities.
  
  
  METHODS
  Amniocentesis was performed on 28 high-risk pregnancies. Amniocytes and the cffDNA fraction were prepared from the amniotic fluid samples. Chromosomal analysis of amniocytes was performed by either karyotyping or single nucleotide polymorphism (SNP) arrays. The corresponding cffDNA samples were blindly analyzed by copy number variation (CNV) sequencing in an independent laboratory.
  
  
  RESULTS
  In the 28 matching amniocyte and cffDNA samples, there was a high diagnostic concordance for detection of euploidy, aneuploidy and CNVs. From ten samples referred for karyotyping, two aneuploidies (20%) were identified. From 18 samples referred for SNP array analysis, three pathogenic CNVs (16.7%) were identified. CNV sequencing of the 28 cffDNA samples also detected the two aneuploidies and the three pathogenic CNVs, giving an overall concordance rate of 100% for detection of pathogenic chromosome abnormalities. Compared with SNP array analysis, CNV sequencing returned a higher yield of benign or variants of unknown significance.
  
  
  CONCLUSIONS
  Copy number variation sequencing of cffDNA represents an alternative approach to conventional prenatal diagnostic methods for reliable and accurate detection of clinically significant chromosomal abnormalities. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Beijing, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Yikon Genomics Co., Ltd, Beijing, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Beijing, China.
authors.forename: Xiya
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Beijing, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Hao
authors.affiliation: Yikon Genomics Co., Ltd, Beijing, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Yin
authors.affiliation: Yikon Genomics Co., Ltd, Beijing, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.affiliation: Becreative Lab Co., Ltd, Beijing, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Bai
authors.affiliation: Becreative Lab Co., Ltd, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Berry Genomics Co., Ltd, Beijing, China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
mesh_terms: D000649:Amniocentesis; D000650:Amnion / Q000166:cytology; D000653:Amniotic Fluid / Q000378:metabolism*; D000782:Aneuploidy; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004314:Down Syndrome / Q000175:diagnosis; D005260:Female; D006801:Humans; D007621:Karyotyping; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA; D014424:Turner Syndrome / Q000175:diagnosis
chemical_list: D004247:DNA