title: Complete discrepancy between QF-PCR analysis of uncultured villi and karyotyping of cultured cells in the prenatal diagnosis of trisomy 21 in three CVS.
abstract: OBJECTIVE
  To investigate complete discrepancies in the prenatal diagnosis of trisomy 21 between QF-PCR analysis of uncultured villi and karyotyping of cultured cells in three chorion villus samples.
  
  
  METHODS
  Clinical details were obtained from all three patients. Follow-up studies were undertaken where possible by evaluation of chromosome 21 copy number with QF-PCR, interphase FISH, MLPA and karyotyping, and by post-mortem examination.
  
  
  RESULTS
  Case 1: severe oligohydramnios and microcephaly on scan. QF-PCR: trisomy 21; MLPA: trisomy 21; cultured karyotype: 46,XY[48]. Placental and fetal tissue results and post-mortem examination indicated a euploid fetus with trisomy 21 mosaicism confined to the placenta. Case 2: Down screen risk 1:16; NT = 4.4 mm; absent nasal bone (Caucasian mother). QF-PCR: disomy 21; cultured karyotype: 47,XY,+ 21[23]. Neck thickening noted at delivery-post-mortem refused, no fetal tissue available. Placental tissue indicated mosaicism for trisomy 21. Case 3: Down screen risk 1:91; NT = 6.7 mm. QF-PCR: disomy 21; cultured karyotype: 46,XX,der(21;21)(q10;q10)[60]. No follow-up possible. PCR genotyping of cultured cells confirmed sample identity in all three cases. Chromosome 21 markers observed by PCR were biallelic in all three cases, indicating that a mitotic error could account for the presence of the abnormal cell lines in each case.
  
  
  CONCLUSIONS
  QF-PCR analysis of uncultured villi and cultured karyotyping may rarely show complete discrepancy in the prediction of fetal trisomy 21 in CVS. Within-biopsy sample mosaicism, together with the testing of different cell populations, provide an explanation for these results. Practical ways to minimise the risk of such discrepancy are proposed.
authors.affiliation: Cytogenetics Laboratory, NE Thames Regional Genetics Service, Gt Ormond St Hospital NHS Trust, London, UK. waterj@gosh.nhs.uk
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Waters
authors.forename: Kathy
authors.initials: K
authors.lastname: Mann
authors.forename: Lee
authors.initials: L
authors.lastname: Grimsley
authors.forename: Caroline Mackie
authors.initials: CM
authors.lastname: Ogilvie
authors.forename: Celia
authors.initials: C
authors.lastname: Donaghue
authors.forename: Leonie
authors.initials: L
authors.lastname: Staples
authors.forename: Alison
authors.initials: A
authors.lastname: Hills
authors.forename: Tracey
authors.initials: T
authors.lastname: Adams
authors.forename: Christine
authors.initials: C
authors.lastname: Wilson
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D015193:Chorionic Villi Sampling; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D016133:Polymerase Chain Reaction / Q000379:methods*; D011247:Pregnancy
chemical_list: D005819:Genetic Markers