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Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes.
Genes (Basel). 2020 11 25; 11(12)G

Abstract

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6-8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2-3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Be Creative Lab Co., Ltd. Beijing 101111, China.AmCare Genomics Lab, Guangzhou 510335, China.Be Creative Lab Co., Ltd. Beijing 101111, China.Be Creative Lab Co., Ltd. Beijing 101111, China.Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.AmCare Genomics Lab, Guangzhou 510335, China.Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33255631

Citation

Qi, Qingwei, et al. "Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses With Ultrasound Anomalies and Normal Karyotypes." Genes, vol. 11, no. 12, 2020.
Qi Q, Jiang Y, Zhou X, et al. Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes. Genes (Basel). 2020;11(12).
Qi, Q., Jiang, Y., Zhou, X., Meng, H., Hao, N., Chang, J., Bai, J., Wang, C., Wang, M., Guo, J., Ouyang, Y., Xu, Z., Xiao, M., Zhang, V. W., & Liu, J. (2020). Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes. Genes, 11(12). https://doi.org/10.3390/genes11121397
Qi Q, et al. Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses With Ultrasound Anomalies and Normal Karyotypes. Genes (Basel). 2020 11 25;11(12) PubMed PMID: 33255631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes. AU - Qi,Qingwei, AU - Jiang,Yulin, AU - Zhou,Xiya, AU - Meng,Hua, AU - Hao,Na, AU - Chang,Jiazhen, AU - Bai,Junjie, AU - Wang,Chunli, AU - Wang,Mingming, AU - Guo,Jiangshan, AU - Ouyang,Yunshu, AU - Xu,Zhonghui, AU - Xiao,Mengsu, AU - Zhang,Victor Wei, AU - Liu,Juntao, Y1 - 2020/11/25/ PY - 2020/09/06/received PY - 2020/11/09/revised PY - 2020/11/16/accepted PY - 2020/12/1/entrez PY - 2020/12/2/pubmed PY - 2021/7/28/medline KW - CMA KW - CNV-seq KW - clinical exome sequencing (CES) KW - fetal ultrasound anomalies KW - prenatal diagnosis JF - Genes JO - Genes (Basel) VL - 11 IS - 12 N2 - The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6-8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2-3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester. SN - 2073-4425 UR - https://www.unboundmedicine.com/medline/citation/33255631/Simultaneous_Detection_of_CNVs_and_SNVs_Improves_the_Diagnostic_Yield_of_Fetuses_with_Ultrasound_Anomalies_and_Normal_Karyotypes_ L2 - https://www.mdpi.com/resolver?pii=genes11121397 DB - PRIME DP - Unbound Medicine ER -