Clinical Selection of Prenatal Diagnostic Techniques Following Positive Noninvasive Prenatal Screening Results in Southwest China

Abstract

Background: This study aims to evaluate prenatal diagnosis methods following positive noninvasive prenatal screening (NIPS) results.Methods: According to the positive noninvasive prenatal screening results, 926 pregnant women were divided into three groups: main target disease group (high risk for trisomy 21, trisomy 18, or trisomy 13), sex chromosome aneuploidy (SCA) group, and other chromosomal abnormalities group [abnormal Z-scores for chromosomes other than trisomy (T)21/T18/T13 or SCAs]. The verification methods and results were then retrospectively analysed.Results: In the main target disease group, the positive rate of chromosomal abnormalities confirmed by quantitative fluorescence polymerase chain reaction (QF-PCR) was 75.18% (212/282), which was not significantly different from that by karyotyping (79.36%, 173/218) and copy number variation (CNV) detection methods (71.43%, 65/91). The positive rate of additional findings confirmed by karyotyping and copy number variation detection methods in main target disease group was 0.46% (1/218) and 8.79% (8/91), respectively. The positive rate of chromosomal abnormalities confirmed by karyotyping and CNV detection methods were 27.11% (45/166) and 38.46% (95/247) in the SCA group and 4.17% (1/24) and 20% (36/180) in the other chromosomal abnormalities group, respectively. Fetal sex chromosome mosaicism was detected in 16.13% (20/124) of the confirmed SCA cases. There were no significant differences in the detection rates of chromosomal microarray analysis (CMA) and CNV sequencing (CNVseq) among the three groups (p > 0.05).Conclusion: QF-PCR can quickly and accurately identify aneuploidies following NIPS-positive results for common aneuploidy, and in combination with karyotyping and CNV detection techniques can provide more comprehensive results. With the NIPS-positive results for SCA or other abnormalities, CMA and CNVseq may have the same effect on increasing the detection rate. The addition of fluorescence in situ hybridization assay may help to identify true fetal mosaicism.

Detecting Mosaicism of Monosomy X Using FISH in Prenatal Samples: Post High Risk NIPT

“…13 Several studies have shown that FISH is better at detecting low level mosaicism. 7,10,14,15 However, the clinical impact of low level mosaicism has to be carefully discussed with the parents. In comparison to nonmosaic monosomy X, the phenotypic symptoms in cases of mosaic monosomy X may be mild, and many cases may even remain undiagnosed.…”

Molecular cytogenetic characterization of a de novo derivative chromosome X with an unbalanced t(X;9) translocation in a fetus and literature review

“…In conclusion, we identified a fetus with 46,X,der(X)t(X;9)(q27;p23)dn suggested by NIPT. Combining cytogenetic study, karyotype analysis, FISH and CNV-seq in prenatal diagnosis of unbalanced X-autosome translation was a reliable method [ 29 ]. We would like to speculate that the fetus would have mild phenotypes, the possible reason might be that 9p23p24.3 is relatively gene poor and the skewed inactivation of abnormal X would spread into the extra segment of chromosome 9 presented in the der(X) resulting a mild phenotype.…”