Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies
ObjectiveThis study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies.MethodsT...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1517270/full |
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| author | Jia-pei Liu Shan-Bing Wang Li Luo Ya-mei Guo |
| author_facet | Jia-pei Liu Shan-Bing Wang Li Luo Ya-mei Guo |
| author_sort | Jia-pei Liu |
| collection | DOAJ |
| description | ObjectiveThis study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies.MethodsThis retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance.ResultsThe integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (p < 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, p < 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes.ConclusionThe integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants. |
| format | Article |
| id | doaj-art-5cc1a1b6efce4c1d9fd454e52610a03a |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-5cc1a1b6efce4c1d9fd454e52610a03a2025-01-13T06:11:49ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.15172701517270Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnanciesJia-pei Liu0Shan-Bing Wang1Li Luo2Ya-mei Guo3Department of Laboratory, The Second People’s Hospital of Yibin City, Yibin, Sichuan, ChinaDepartment of Oncology Medicine, The Second People’s Hospital of Yibin City, Yibin, Sichuan, ChinaDepartment of Laboratory, The Second People’s Hospital of Yibin City, Yibin, Sichuan, ChinaDepartment of Laboratory, The Second People’s Hospital of Yibin City, Yibin, Sichuan, ChinaObjectiveThis study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies.MethodsThis retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance.ResultsThe integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (p < 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, p < 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes.ConclusionThe integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants.https://www.frontiersin.org/articles/10.3389/fgene.2024.1517270/fullchromosomal abnormalitiesprenatal diagnosiskaryotypingCNV-seqQF-PCRhigh-risk pregnancy |
| spellingShingle | Jia-pei Liu Shan-Bing Wang Li Luo Ya-mei Guo Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies Frontiers in Genetics chromosomal abnormalities prenatal diagnosis karyotyping CNV-seq QF-PCR high-risk pregnancy |
| title | Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies |
| title_full | Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies |
| title_fullStr | Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies |
| title_full_unstemmed | Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies |
| title_short | Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies |
| title_sort | improving prenatal diagnosis with combined karyotyping cnv seq and qf pcr a comprehensive analysis of chromosomal abnormalities in high risk pregnancies |
| topic | chromosomal abnormalities prenatal diagnosis karyotyping CNV-seq QF-PCR high-risk pregnancy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1517270/full |
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