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Prenatal trio-based whole exome sequencing in fetuses with abnormalities of the skeletal system

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Abstract

Whole exome sequencing (WES) could yield diagnostic significance in the prenatal diagnosis of skeletal abnormalities. But the phenotypes of fetuses with skeletal abnormalities are heterogenous, and the clinical information we could obtain from an ongoing pregnancy is limited, making the prenatal diagnosis complicated. Therefore, the following interpretation and genetic counseling remain a challenge for clinicians. The aim of this study is to present and investigate the utility of trio-based WES in five fetuses with skeletal anomalies. Five trios with fetal ultrasonic skeletal anomalies were recruited in our study. Fetal specimens and parental peripheral blood were subjected to WES. The fetal skeletal abnormalities were presented through ultrasound scanning images. Fetal WES results showed variants in the PPIB, CHST3, COL1A1, and FGFR3 genes in the five trios. Inherited variants were found in two of the trios, while de novo variants were observed in three of them. Two novel compound heterozygous variants (c.437C > A and c.1044C > G) in CHST3 were identified. We presented five trios with fetal skeletal anomalies, found two novel variants and broadened the spectrum of variants associated with skeletal abnormalities, which would help the establishment of genotype–phenotype relationship in the prenatal setting. Trio-based WES could assist the prenatal diagnosis and genetic counseling of fetuses with skeletal abnormalities.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

No funding was received for conducting this study.

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Authors and Affiliations

  1. Prenatal Diagnosis Center, Hangzhou Maternity and Child Care Hospital, 369 Kunpeng Road, Shangcheng District, Hangzhou, 310008, Zhejiang, China

    Yang Yang, Min Wang & Hao Wang

  2. Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Hao Wang

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  1. Yang Yang
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  2. Min Wang
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  3. Hao Wang
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Contributions

Y:Y drafted the manuscript. MW: acquired the clinic data. HW: analyzed and interpreted the patient data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hao Wang.

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The authors declare that they have no conflict of Interest.

Ethical approval

This retrospective chart review study involving human participants was approved by the Ethics Committee of Hangzhou Maternity and Child Care Hospital and was in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Written informed consent was obtained from the parents.

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The patients had provided their consent for publication.

Additional information

Communicated by Shuhua Xu.

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Yang, Y., Wang, M. & Wang, H. Prenatal trio-based whole exome sequencing in fetuses with abnormalities of the skeletal system. Mol Genet Genomics 297, 1017–1026 (2022). https://doi.org/10.1007/s00438-022-01899-x

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