Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases. 2023

Yayun Qin, and Yanyi Yao, and Nian Liu, and Bo Wang, and Lijun Liu, and Hui Li, and Tangxinzi Gao, and Runhong Xu, and Xiaoyan Wang, and Fanglian Zhang, and Jieping Song
Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, Hubei Province, China.

Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses. We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported. In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes. Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011261 Pregnancy Trimester, First The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation. Early Placental Phase,Pregnancy, First Trimester,Trimester, First,Early Placental Phases,First Pregnancy Trimester,First Pregnancy Trimesters,First Trimester,First Trimester Pregnancies,First Trimester Pregnancy,First Trimesters,Phase, Early Placental,Phases, Early Placental,Placental Phase, Early,Placental Phases, Early,Pregnancies, First Trimester,Pregnancy Trimesters, First,Trimesters, First
D011296 Prenatal Diagnosis Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth. Diagnosis, Prenatal,Fetal Diagnosis,Fetal Imaging,Fetal Screening,Intrauterine Diagnosis,Antenatal Diagnosis,Antenatal Screening,Diagnosis, Antenatal,Diagnosis, Intrauterine,Prenatal Screening,Antenatal Diagnoses,Antenatal Screenings,Diagnosis, Fetal,Fetal Diagnoses,Fetal Imagings,Fetal Screenings,Imaging, Fetal,Intrauterine Diagnoses,Prenatal Diagnoses,Prenatal Screenings,Screening, Antenatal,Screening, Fetal,Screening, Prenatal
D005260 Female Females
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000013 Congenital Abnormalities Malformations of organs or body parts during development in utero. Birth Defects,Congenital Defects,Deformities,Fetal Anomalies,Fetal Malformations,Abnormalities, Congenital,Defects, Congenital,Abnormality, Congenital,Anomaly, Fetal,Birth Defect,Congenital Abnormality,Congenital Defect,Defect, Birth,Defect, Congenital,Deformity,Fetal Anomaly,Fetal Malformation,Malformation, Fetal
D000073359 Exome Sequencing Techniques used to determine the sequences of EXONS of an organism or individual. Complete Exome Sequencing,Complete Transcriptome Sequencing,Whole Exome Sequencing,Whole Transcriptome Sequencing,Complete Exome Sequencings,Exome Sequencing, Complete,Exome Sequencing, Whole,Exome Sequencings, Complete,Sequencing, Complete Exome,Sequencing, Complete Transcriptome,Sequencing, Exome,Sequencing, Whole Exome,Sequencing, Whole Transcriptome,Transcriptome Sequencing, Complete,Transcriptome Sequencing, Whole,Transcriptome Sequencings, Complete
D000095225 East Asian People East Asians,Eastern Asian People,Eastern Asians,Far East Asians,Chinese,Japanese,Koreans,Asian People, East,Asian People, Eastern,Asian, East,Asian, Eastern,Asian, Far East,East Asian,East Asian Peoples,Eastern Asian,Eastern Asian Peoples,Far East Asian,People, East Asian,People, Eastern Asian
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective

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