Dataset Information

Prenatal diagnosis of 913 fetuses samples using copy number variation sequencing.

ABSTRACT:

Background

The present study aimed to explore the etiological relationship between fetal abnormalities and copy number variations (CNVs) with the aim of intervening and preventing the birth of children with birth defects in time.

Methods

Samples of 913 fetuses with puncture indications were collected from January 2017 to December 2019. Karyotype analysis and CNV sequencing (CNV-seq) testing was performed for fetuses with ultrasonic abnormalities, a high risk of Down's syndrome and an adverse birth history. All cases were followed up.

Results

In total, 123 cases (13.47%) had abnormal karyotypes, including 109 cases with chromosome number abnormalities and 14 cases of chromosomal structural abnormalities. Thirty-seven (4.05%) cases with pathogenic CNVs were detected. The detection rate of pathogenicity CNVs was 12.82% for mixed indications, followed by 7.5% for an adverse birth history, 5.88% at high risk of non-invasive prenatal testing, 5.00% with an abnormal ultrasonic marker, 1.89% at high risk of screening for Down's syndrome and 1.45% with advanced maternal age. There were 12 (1.31%) cases with microduplications and 25 (2.74%) cases with microdeletions. Trisomy 21 (39.02%), trisomy 18 (13.82%) and Turner syndrome (9.76%) were the top three chromosome abnormalities. There were 104, 746 and 63 cases in the 11-13 weeks, 14-27 weeks 28-38 weeks gestational ages, respectively. The abnormal rates of fetal chromosome aneuploidy and the rate of pathogenic CNVs were decreased and increased with the increase of gestational age (p < 0.05), respectively.

Conclusions

Compared with karyotype analysis, CNV-seq can improve the detection rate of chromosomal abnormalities. CNV-seq combined karyotype analysis should be performed simultaneously in fetuses with puncture indications.

SUBMITTER: Lan L

PROVIDER: S-EPMC8243933 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundKaryotyping and genome copy number variation sequencing (CNV-seq) are two techniques frequently used in prenatal diagnosis. This study aimed to explore the diagnostic potential of using a combination of these two methods in order to provide a more accurate clinical basis for prenatal diagnosis.MethodsWe selected 822 pregnant women undergoing amniocentesis and separated them into six groups according to different risk indicators. Karyotyping and CNV-seq were performed simultaneously to compare the diagnostic performance of the two methods.ResultsAmong the different amniocentesis indicators, abnormal fetal ultrasounds accounted for 39.29% of the total number of examinees and made up the largest group. The abnormal detection rate of non-invasive prenatal testing (NIPT) high risk was 37.93% and significantly higher than the other five groups (P < 0.05). The abnormal detection rate of mixed indicators was significantly higher than the history of the adverse reproductive outcomes group (P = 0.0151). The two methods combined found a total of 119 abnormal cases (14.48%). Karyotyping detected 57 cases (6.93%) of abnormal karyotypes, 30 numerical aberrations, and 27 structural aberrations. CNV-seq identified 99 cases (12.04%) with altered CNVs, 30 cases of chromosome aneuploidies, and 69 structural aberrations (28 pathogenic, eight that were likely pathogenic, and 33 microdeletion/duplication variants of uncertain significance (VUS)). Thirty-seven cases were found abnormal by both methods, 20 cases were detected abnormally by karyotyping (mainly mutual translocation and mostly balanced), and 62 cases of microdeletion/duplication were detected by CNV-seq. Steroid sulfatase gene (STS) deletion was identified at chromosome Xp22.31 in three cases. Postnatal follow-up confirmed that babies manifested skin abnormalities one week after birth. Six fetuses had Xp22.31 duplications ranging from 1.5 Kb to 1.7 Mb that were detected by CNV-seq. Follow-up showed that five babies presented no abnormalities during follow-up, except for one terminated pregnancy due to a history of adverse reproductive outcomes.ConclusionThe combination of using CNV-seq and karyotyping significantly improved the detection rate of fetal pathogenic chromosomal abnormalities. CNV-seq is an effective complement to karyotyping and improves the accuracy of prenatal diagnosis.