Is routine karyotyping required in prenatal samples with a molecular or metabolic referral?

Abstract

As a routine, karyotyping of invasive prenatal samples is performed as an adjunct to referrals for DNA mutation detection and metabolic testing. We performed a retrospective study on 500 samples to assess the diagnostic value of this procedure. These samples included 454 (90.8%) chorionic villus (CV) and 46 (9.2%) amniocenteses specimens. For CV samples karyotyping was based on analyses of both short-term culture (STC) and long-term culture (LTC) cells. Overall, 19 (3.8%) abnormal karyotypes were denoted: four with a common aneuploidy (trisomy 21, 18 and 13), two with a sex chromosomal aneuploidy (Klinefelter syndrome), one with a sex chromosome mosaicism and twelve with various autosome mosaicisms. In four cases a second invasive test was performed because of an abnormal finding in the STC. Taken together, we conclude that STC and LTC karyotyping has resulted in a diagnostic yield of 19 (3.8%) abnormal cases, including 12 cases (2.4%) with an uncertain significance. From a diagnostic point of view, it is desirable to limit uncertain test results as secondary test findings. Therefore, we recommend a more targeted assay, such as e.g. QF-PCR, as a replacement of the STC and to provide parents the autonomy to choose between karyotyping and QF-PCR.

Whole‐genome array as a first‐line cytogenetic test in prenatal diagnosis

“…1:200 general population risk for a submicroscopic clinically significant chromosomal abnormality. Once the miscarriage risk of the invasive sampling procedure has been accepted, a SNP array (with minimum 0.5‐Mb resolution) should be considered, although it has been suggested that standalone RAD would be sufficient for such an indication.…”

Is prenatal cytogenetic diagnosis with genomic array indicated in pregnancies at risk for a molecular or metabolic disorder?

“…A few years ago, several laboratories introduced rapid aneuploidy testing for detection of trisomy 13, 18, and 21, triploidy, and aneuploidy of sex chromosomes as a standalone test for molecular and metabolic referrals. 1,2 Recent advances in microarray testing in pregnancies without ultrasound anomalies led to new insights into the prevalence of submicroscopic chromosome aberrations in such fetuses. Some large-scale studies showed a significant percentage (0.5%) of pathogenic submicroscopic findings in pregnancies tested due to advanced maternal age or abnormal first-trimester screening.…”

Evaluation of Quantitative Fluorescence in situ Hybridization for Relative Measurement of Telomere Length in Placental Mesenchymal Core Cells

“…These cells had undergone a double enzymatic treatment (trypsin then collagenase) identical to that used before culture of the placental villi. Enzymatic dissociation with trypsin followed by collagenase has been shown to isolate cell populations consisting predominantly of cells from the mesenchymal core [23,24,25,26,27]. In the uncultured cells, the distribution of fluorescence intensity was normal (fig.…”

“…In order to isolate a large majority of placental mesenchymal core cells, placental villi underwent a double enzymatic treatment [23,25]. First, a trypsin-EDTA solution (Sigma-Aldrich, St. Louis, Mo., USA) was applied for 20-30 min; second, a collagenase solution (Sigma-Aldrich) was applied for 30-60 min, depending on the quantity of villi.…”