title: Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.
abstract: OBJECTIVE
  To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients.
  
  
  METHODS
  This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options.
  
  
  RESULTS
  Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases.
  
  
  CONCLUSIONS
  Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure.
authors.affiliation: Prenatal Diagnosis Center, Department of Gynecology & Obstetrics, Southwest Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: H
authors.initials: H
authors.lastname: Yao
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Yuan
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Du
authors.forename: N
authors.initials: N
authors.lastname: Qu
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Dong
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Tian
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D002681:China; D025063:Chromosome Disorders / Q000175:diagnosis; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D004314:Down Syndrome / Q000175:diagnosis; D005240:Feasibility Studies; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D062145:Maternal Serum Screening Tests; D008875:Middle Aged; D011247:Pregnancy; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods*; D012729:Sex Chromosome Aberrations; D014314:Trisomy / Q000175:diagnosis; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D055815:Young Adult
keywords: clinical counseling; fetal DNA; massively parallel sequencing; maternal serum; prenatal screening test; sex chromosome aneuploidy