title: Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA analysis.
abstract: OBJECTIVE
  To examine the performance of chromosome-selective sequencing of cell-free (cf) DNA in maternal blood for assessment of fetal sex chromosome aneuploidies.
  
  
  METHODS
  This was a case-control study of 177 stored maternal plasma samples, obtained before fetal karyotyping at 11-13 weeks of gestation, from 59 singleton pregnancies with fetal sex chromosome aneuploidies (45,X, n = 49; 47,XXX, n = 6; 47,XXY, n = 1; 47,XYY, n = 3) and 118 with euploid fetuses (46,XY, n = 59; 46,XX, n = 59). Digital analysis of selected regions (DANSR™) on chromosomes 21, 18, 13, X and Y was performed and the fetal-fraction optimized risk of trisomy evaluation (FORTE™) algorithm was used to estimate the risk for non-disomic genotypes. Performance was calculated at a risk cut-off of 1:100.
  
  
  RESULTS
  Analysis of cfDNA provided risk scores for 172 (97.2%) samples; 4 samples (45,X, n = 2; 46,XY, n = 1; 46,XX, n = 1) had an insufficient fetal cfDNA fraction for reliable testing and 1 case (47,XXX) failed laboratory quality control metrics. The classification was correct in 43 (91.5%) of 47 cases of 45,X, all 5 of 47,XXX, 1 of 47,XXY and 3 of 47,XYY. There were no false-positive results for monosomy X.
  
  
  CONCLUSIONS
  Analysis of cfDNA by chromosome-selective sequencing can correctly classify fetal sex chromosome aneuploidy with reasonably high sensitivity.
authors: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors: Kypros H
authors: KH
authors: Nicolaides
authors: Thomas J
authors: TJ
authors: Musci
authors: Craig A
authors: CA
authors: Struble
authors: Argyro
authors: A
authors: Syngelaki
authors: M M
authors: MM
authors: Gil
mesh_terms: D000782:Aneuploidy; D016022:Case-Control Studies; D025063:Chromosome Disorders / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007621:Karyotyping; D062145:Maternal Serum Screening Tests / Q000379:methods*; D011247:Pregnancy; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D012730:Sex Chromosomes