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Whole exome sequencing of fetal structural anomalies detected by ultrasonography

Journal of Human Genetics volume 66, pages 499–507 (2021)Cite this article

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Abstract

The objective of this study was to evaluate the efficacy of whole exome sequencing (WES) for the genetic diagnosis of cases presenting with fetal structural anomalies detected by ultrasonography. WES was performed on 19 cases with prenatal structural anomalies. Genomic DNA was extracted from umbilical cords or umbilical blood obtained shortly after birth. WES data were analyzed on prenatal phenotypes alone, and the data were re-analyzed after information regarding the postnatal phenotype was obtained. Based solely on the fetal phenotype, pathogenic, or likely pathogenic, single nucleotide variants were identified in 5 of 19 (26.3%) cases. Moreover, we detected trisomy 21 in two cases by WES-based copy number variation analysis. The overall diagnostic rate was 36.8% (7/19). They were all compatible with respective fetal structural anomalies. By referring to postnatal phenotype information, another candidate variant was identified by a postnatal clinical feature that was not detected in prenatal screening. As detailed phenotyping is desirable for better diagnostic rates in WES analysis, we should be aware that fetal phenotype is a useful, but sometimes limited source of information for comprehensive genetic analysis. It is important to amass more data of genotype–phenotype correlations, especially to appropriately assess the validity of WES in prenatal settings.

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Acknowledgements

We would like to thank the patients and their families for participating in this study. We also thank N. Watanabe, T. Miyama, M. Sato, S. Sugimoto, and K. Takabe for their technical assistance. This work was supported by Japan Agency for Medical Research and Development (AMED) under grant numbers JP19ek0109280, JP19dm0107090, JP19ek0109301, JP19ek0109348, and JP19kk0205001; by Japan Society for the Promotion of Science (JSPS) KAKENHI under grant numbers JP17H01539, JP16H05357, JP16H06254, JP17K16132, JP17K10080, JP17K15630, and JP17H06994; by the Ministry of Health, Labour and Welfare under intramural grant numbers 30-6 and 30-7; and by the Takeda Science Foundation. We thank Edanz Group (www.edanzediting.com) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Hiromi Aoi, Takeshi Mizuguchi, Rie Seyama, Yuri Uchiyama, Yoshiteru Azuma, Kohei Hamanaka, Atsushi Fujita, Eriko Koshimizu, Satoko Miyatake, Satomi Mitsuhashi, Atsushi Takata, Noriko Miyake & Naomichi Matsumoto

  2. Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan

    Hiromi Aoi, Toshifumi Suzuki, Shintaro Makino, Yuka Yamamoto, Jun Takeda, Yojiro Maruyama, Rie Seyama, Shiori Takeuchi, Satoru Takeda & Atsuo Itakura

  3. Department of Obstetrics and Gynecology, Keiai Hospital, Saitama, Japan

    Toshifumi Suzuki

  4. Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Yuri Uchiyama

  5. Department of Clinical Genetics, Graduate School of Medicine, Yokohama City University Hospital, Yokohama, Japan

    Satoko Miyatake

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  1. Hiromi Aoi
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Correspondence to Naomichi Matsumoto.

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Aoi, H., Mizuguchi, T., Suzuki, T. et al. Whole exome sequencing of fetal structural anomalies detected by ultrasonography. J Hum Genet 66, 499–507 (2021). https://doi.org/10.1038/s10038-020-00869-8

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