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Clinical application of medical exome sequencing for prenatal diagnosis of fetal structural anomalies.
Eur J Obstet Gynecol Reprod Biol. 2020 Aug; 251:119-124.EJ

Abstract

OBJECTIVE

To evaluate the clinical application of medical exome sequencing (MES) for prenatal diagnosis of genetic diseases related to fetal structural anomalies detected by prenatal ultrasound examination.

STUDY DESIGN

A total of 105 fetuses with structural anomalies were negative results in both Quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA). Then trio-based MES was further used for identifying the potential monogenic diseases in these fetuses. Coding regions and known pathogenic non-coding regions of over 4000 disease-related genes were interrogated, and variants were classified following the guidelines of American College of Medical Genetics (ACMG).

RESULTS

The 105 fetuses with structural anomalies were categorized into 12 phenotypic groups. A definitive diagnosis was achieved in 19% (20/105) of the cases, with the identification of 21 pathogenic or likely pathogenic variants in 14 genes. The proportion of patients with diagnostic genetic variants varied between the phenotypic groups, with the highest diagnostic yield in the cardiovascular abnormalities (44%), followed by the skeletal and limb abnormalities (38%) and brain structural abnormalities (25%). In addition, 12 fetuses were detected variants of unknown significance (VOUS), while the relevance of phenotypes and variants would further evaluated.

CONCLUSION

MES can identify the underlying genetic cause in fetal structural anomalies. It can further assist the management of pregnancy and genetic counseling. It was demonstrated the importance of translating prenatal MES into clinical practice.

Authors+Show Affiliations

Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes. Electronic address: edchen99@gmail.com.Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.AmCare Genomics Laboratory, Guangzhou, 510300, Guangdong, China.Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.AmCare Genomics Laboratory, Guangzhou, 510300, Guangdong, China.AmCare Genomics Laboratory, Guangzhou, 510300, Guangdong, China; Baylor College of Medicine, Department of Human and Molecular Genetics, Houston, USA.Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32502767

Citation

Chen, Min, et al. "Clinical Application of Medical Exome Sequencing for Prenatal Diagnosis of Fetal Structural Anomalies." European Journal of Obstetrics, Gynecology, and Reproductive Biology, vol. 251, 2020, pp. 119-124.
Chen M, Chen J, Wang C, et al. Clinical application of medical exome sequencing for prenatal diagnosis of fetal structural anomalies. Eur J Obstet Gynecol Reprod Biol. 2020;251:119-124.
Chen, M., Chen, J., Wang, C., Chen, F., Xie, Y., Li, Y., Li, N., Wang, J., Zhang, V. W., & Chen, D. (2020). Clinical application of medical exome sequencing for prenatal diagnosis of fetal structural anomalies. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 251, 119-124. https://doi.org/10.1016/j.ejogrb.2020.04.033
Chen M, et al. Clinical Application of Medical Exome Sequencing for Prenatal Diagnosis of Fetal Structural Anomalies. Eur J Obstet Gynecol Reprod Biol. 2020;251:119-124. PubMed PMID: 32502767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical application of medical exome sequencing for prenatal diagnosis of fetal structural anomalies. AU - Chen,Min, AU - Chen,Jingsi, AU - Wang,Chunli, AU - Chen,Fei, AU - Xie,Yinong, AU - Li,Yufan, AU - Li,Nan, AU - Wang,Jing, AU - Zhang,Victor Wei, AU - Chen,Dunjin, Y1 - 2020/05/20/ PY - 2020/01/26/received PY - 2020/04/13/revised PY - 2020/04/15/accepted PY - 2020/6/6/pubmed PY - 2021/5/15/medline PY - 2020/6/6/entrez KW - Genomic variants KW - Medical Exome Sequencing KW - Next-generation sequencing KW - Prenatal diagnosis KW - fetal structural anomalies KW - whole-exome sequencing SP - 119 EP - 124 JF - European journal of obstetrics, gynecology, and reproductive biology JO - Eur J Obstet Gynecol Reprod Biol VL - 251 N2 - OBJECTIVE: To evaluate the clinical application of medical exome sequencing (MES) for prenatal diagnosis of genetic diseases related to fetal structural anomalies detected by prenatal ultrasound examination. STUDY DESIGN: A total of 105 fetuses with structural anomalies were negative results in both Quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA). Then trio-based MES was further used for identifying the potential monogenic diseases in these fetuses. Coding regions and known pathogenic non-coding regions of over 4000 disease-related genes were interrogated, and variants were classified following the guidelines of American College of Medical Genetics (ACMG). RESULTS: The 105 fetuses with structural anomalies were categorized into 12 phenotypic groups. A definitive diagnosis was achieved in 19% (20/105) of the cases, with the identification of 21 pathogenic or likely pathogenic variants in 14 genes. The proportion of patients with diagnostic genetic variants varied between the phenotypic groups, with the highest diagnostic yield in the cardiovascular abnormalities (44%), followed by the skeletal and limb abnormalities (38%) and brain structural abnormalities (25%). In addition, 12 fetuses were detected variants of unknown significance (VOUS), while the relevance of phenotypes and variants would further evaluated. CONCLUSION: MES can identify the underlying genetic cause in fetal structural anomalies. It can further assist the management of pregnancy and genetic counseling. It was demonstrated the importance of translating prenatal MES into clinical practice. SN - 1872-7654 UR - https://www.unboundmedicine.com/medline/citation/32502767/Clinical_application_of_medical_exome_sequencing_for_prenatal_diagnosis_of_fetal_structural_anomalies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-2115(20)30218-9 DB - PRIME DP - Unbound Medicine ER -