Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Discrepancy between non-invasive prenatal testing result and fetal karyotype caused by rare confined placental mosaicism: A case report

BACKGROUND Confined placental mosaicism(CPM)is one of the major reasons for discrepancies between the results of non-invasive prenatal testing(NIPT)and fetal karyotype analysis.CASE SUMMARY We encountered a primiparous singleton pregnant woman with a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,who obtained a false-positive result on NIPT with a high risk for trisomy 21.Copy-number variation sequencing on amniotic fluid cells,fetal tissue,and placental biopsies showed that the fetal karyotype was 47,XXY,while the placenta was a rare mosaic of 47,XY,+21;47,XXY;and 46,XY.CONCLUSION The patient had a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,which caused a discrepancy between the result of NIPT and the actual fetal karyotype.It is important to remember that NIPT is a screening test,not a diagnostic test.Any positive result should be confirmed with invasive testing,and routine ultrasound examination is still necessary after a negative result.

Comparison of next generation sequencing-based and methylated DNA immunoprecipitation-based approaches for fetal aneuploidy non-invasive prenatal testing

Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.

New mechanism of partial duplication and deletion of chromosome 8:A case report

BACKGROUND During meiosis,the recombination of homologous chromosomes produces some new heritable mutations,which are the basis of biological evolution and diversity.However,when there is pericentric inversion of chromosomes,unbalanced gametes will be formed in the process of germ cell meiosis.CASE SUMMARY A 23-year-old pregnant woman at 25 wk of gestation wanted to terminate her pregnancy due to fetal chromosomal abnormalities.She had no exposure to toxic or hazardous substances before and during pregnancy,no history of medication usage during pregnancy,and she underwent cystectomy of ovarian cysts in 2017.On the second day of the 16th week of gestation,non-invasive prenatal testing showed chromosome 8 copy number variation.Following genetic counseling,her pregnancy was terminated.CONCLUSION Recombinant offspring chromosome is rarely seen when the inversion segment is shorter than one-third of the chromosome length.In terms of the mechanism of chromosome 8 duplication/deletion occurrence,attention should be paid to the production of unbalanced gametes by the pairing of homologous chromosome during meiosis,and the possibility of mitotic recombination exchange as well.

Short-DNA Specific Blocker PCR for Efficient and Simple Enrichment of Cell Free Fetal DNAs with Short Lengths

As an inn ate characteristic,DNA length has attracted more and more atte ntion.The length of some import ant biomarkers such as ctDNA(Circulating tumor DNA)and cffDNA(Cell free fetal DNA)is shorter than that of cell-free DNA.Researchers have utilized the differe nee in length to in crease the abunda nee of ctDNA or cffDNA in total cell-free DNA to overcome the difficulties in detecti on due to their low abundance.