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Open Access 01-12-2019 | Trisomy 18 | Research

Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases

Authors: Yan Liu, Li Wang, Yi-Ke Yang, Ying Liang, Tie-Juan Zhang, Na Liang, Li-Man Yang, Si-Jing Li, Dan Shan, Qing-Qing Wu

Published in: Diagnostic Pathology | Issue 1/2019

Abstract

Background

This study aims to provide genetic diagnoses for 30 cases of fetal skeletal dysplasia, and a molecular basis for the future prenatal diagnosis of fetal skeletal dysplasia.

Methods

A total of 30 cases of fetal skeletal dysplasia detected with ultrasound between January 2014 and June 2017 were analyzed. Among these fetuses, 15 fetuses had local skeletal malformations, while 15 fetuses had short limb malformations. Samples of fetal umbilical cord blood, amniotic fluid, and/or aborted tissue were collected from all cases. Karyotyping, whole genome sequencing, and targeted next-generation sequencing of skeletal disease-related pathogenic genes were performed, as needed. Blood samples were taken from the parents for verification using Sanger sequencing.

Results

Among the 30 cases of fetal skeletal dysplasia, two cases were diagnosed with trisomy 18. However, none of these cases were identified with any microdeletions or microreplications associated with skeletal dysplasia. Among the 28 chromosomally normal cases with fetal skeletal dysplasia, 21 cases were detected with mutations in genes related to skeletal diseases. Furthermore, collagen gene mutations were detected in six fetuses with short limb malformations, while heterozygous disease-causing mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were detected in seven fetuses. The remaining fetuses carried mutations in other various genes, including tumor protein p63 (TP63), cholestenol delta-isomerase (EBP), cholinergic receptor nicotinic gamma subunit (CHRNG), filamin B (FLNB), and SRY-box 9 (SOX9). Three compound heterozygous mutations in CHRNG, COL11A2 and SOX9 were carried by phenotypically healthy parents.

Conclusion

Targeted next-generation sequencing can significantly improve the prenatal diagnoses of fetal skeletal dysplasia, providing parents with more precision medicine, and improved genetic counseling.

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Title: Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases
Authors: Yan Liu
Li Wang
Yi-Ke Yang
Ying Liang
Tie-Juan Zhang
Na Liang
Li-Man Yang
Si-Jing Li
Dan Shan
Qing-Qing Wu
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Trisomy 18
Published in: Diagnostic Pathology / Issue 1/2019
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-019-0853-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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