Whole genome sequencing vs chromosomal microarray analysis in prenatal diagnosis - 25/08/23
, Fengchang Qiao, PhD ⁎ , Zhengfeng Xu, MD ⁎ Abstract |
Background |
Emerging studies suggest that whole genome sequencing provides additional diagnostic yield of genomic variants when compared with chromosomal microarray analysis in the etiologic diagnosis of infants and children with suspected genetic diseases. However, the application and evaluation of whole genome sequencing in prenatal diagnosis remain limited.
Objective |
This study aimed to evaluate the accuracy, efficacy, and incremental yield of whole genome sequencing in comparison with chromosomal microarray analysis for routine prenatal diagnosis.
Study Design |
In this prospective study, a total of 185 unselected singleton fetuses with ultrasound-detected structural anomalies were enrolled. In parallel, each sample was subjected to whole genome sequencing and chromosomal microarray analysis. Aneuploidies and copy number variations were detected and analyzed in a blinded fashion. Single nucleotide variations and insertions and deletions were confirmed by Sanger sequencing, and trinucleotide repeats expansion variants were verified using polymerase chain reaction plus fragment-length analysis.
Results |
Overall, genetic diagnoses using whole genome sequencing were obtained for 28 (15.1%) cases. Whole genome sequencing not only detected all these aneuploidies and copy number variations in the 20 (10.8%) diagnosed cases identified by chromosomal microarray analysis, but also detected 1 case with an exonic deletion of COL4A2 and 7 (3.8%) cases with single nucleotide variations or insertions and deletions. In addition, 3 incidental findings were detected including an expansion of the trinucleotide repeat in ATXN3, a splice-sites variant in ATRX, and an ANXA11 missense mutation in a case of trisomy 21.
Conclusion |
Compared with chromosomal microarray analysis, whole genome sequencing increased the additional detection rate by 5.9% (11/185). Using whole genome sequencing, we detected not only aneuploidies and copy number variations, but also single nucleotide variations and insertions and deletions, trinucleotide repeat expansions, and exonic copy number variations with high accuracy in an acceptable turnaround time (3–4 weeks). Our results suggest that whole genome sequencing has the potential to be a new promising prenatal diagnostic test for fetal structural anomalies.
Le texte complet de cet article est disponible en PDF.Key words : chromosomal microarray analysis, exonic deletion, fetal structural anomalies, prenatal diagnosis, trinucleotide repeat expansion, whole genome sequencing
Plan
| P.H., Q.Z., and Q.C. contributed equally to this work. |
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| The authors report no conflict of interest. |
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| This study was supported by the National Key R&D Program of China under grant numbers 2022YFC2703400 to Z.X. and P.H. and 2021YFC1005301 to P.H., the National Natural Science Foundation of China under grant numbers 81971398 to P.H., 82101943 to Q.Z., and 82103927 to M.H., the Natural Science Foundation of Jiangsu Province under grant number BK20210037 to M.H., the Maternal and Children Health Project of Jiangsu Province under grant number F202158 to F.Q., and the Scientific Research Project of Jiangsu Maternal and Children Health Care Association under grant number FYX202118 to F.Q. |
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| The research ethics committee of the Nanjing Maternity and Child Health Care Hospital approved the study ([2019]KY-080) in accordance with the Helsinki Declaration of 1975, as revised in 2000. |
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| Informed consent was obtained from all the study participants at the time of providing samples. |
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| Cite this article as: Hu P, Zhang Q, Cheng Q, et al. Whole genome sequencing vs chromosomal microarray analysis in prenatal diagnosis. Am J Obstet Gynecol 2023;229:302.e1-18. |
Vol 229 - N° 3
P. 302.e1-302.e18 - septembre 2023 Retour au numéro
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