Complete discrepancy between abnormal fetal karyotypes predicted by QF‐PCR rapid testing and karyotyped cultured cells in a first‐trimester CVS

Abstract

A chorion villus sample (CVS) biopsied at 11 weeks' gestation for raised nuchal translucency, revealed monosomy X (presumptive 45,X karyotype) by QF-PCR for rapid aneuploidy testing for chromosomes 13, 18, 21, X and Y. Long-term culture gave the karyotype: 47,XY,+ 21[66]/49,XYY,+ 21,+ 21 [22]. This discrepancy prompted redigestion of the combined residual villus fragments from the original QF-PCR assay. The repeat QF-PCR assay identified the presence of trisomy 21 and a Y chromosome consistent with a 47,XY,+ 21 karyotype. A double non-disjunction event early in embryogenesis in a 47,XY,+ 21 conceptus with subsequent cell lineage compartmentalisation of the three observed cell lines (45,X; 47,XY,+ 21 and 49,XYY,+ 21,+ 21) would account for these results. This is the first reported case to describe complete discrepancy at diagnosis between abnormal karyotypes detected by QF-PCR rapid aneuploidy testing and a cultured karyotype in the same CVS.

QF‐PCR: application, overview and review of the literature

“…Complete discrepancies are of greater concern; regarding AFs, there have been no reported complete discrepancies between a diagnostic QF‐PCR and karyotype result for autosomal trisomies although one group has reported a discrepant sex test result (XX on PCR, X/XXX on karyotype) . Diagnoses for CVS are more problematic, with reports of completely discrepant QF‐PCR and karyotype results due to placental mosaicism from a number of centres . The incidence of such discrepant results is likely to be determined by several factors, including the following: The quality and size of the original CV biopsy .…”

Quantitative fluorescent polymerase chain reaction for rapid prenatal diagnosis of fetal aneuploidies in chorionic villus sampling in a single institution

“…QF-PCR can detect mosaicisms with low-level trisomy cell lines [19]. To date, only a few case reports of complete discrepancies between diagnostic QF-PCR and CVS karyotyping results for common selected autosomal trisomies of chromosomes 13, 18, and 21 have been reported [678920]. In the past, the incidence of true false-negative CVS results by short-term culture and LTC was estimated to be lower than 0.03% (1 in 3,300) [21].…”

“…QF-PCR has been widely used in most developed countries, but the efficacy of CVS with QF-PCR has not been validated in Korea. To date, only a few case reports of complete discrepancies between diagnostic QF-PCR and CVS karyotyping results for common selected autosomal trisomies of chromosomes 13, 18, and 21 have been described [6789] and there have been no reports on QF-PCR by CVS in Korea. Therefore, the primary outcome of this study was the detection rate of the common aneuploidies with trisomies 13, 18, and 21 by QF-PCR via CVS.…”

The Replacement of Cytogenetic Analysis by Direct Chorionic Villi Sampling Preparation with Quantitative Fluorescence PCR

“…It has also been shown that QF-PCR cannot detect mosaicism at a level lower than 15%, which is rarely the case when full cytogenetic analysis is performed in LTC [4,27] . In our study the discrepancies between the QF-PCR and LTC results in the cases of mos +21, ( table 3 ; cases 1 and 2) and mos 45,X/46,XY ( table 3 ; case 3) could be attributed to sampling from different sites of a mosaic placenta and testing or culturing different cell populations.…”

“…A complete discrepancy in the prediction of fetal trisomies 18 and 21 in CVS by QF-PCR analysis of uncultured villi and karyotyping after LTC is rare, but it has been reported in certain cases [26][27][28][29] . It has also been shown that QF-PCR cannot detect mosaicism at a level lower than 15%, which is rarely the case when full cytogenetic analysis is performed in LTC [4,27] .…”