Introduction
Fetal skeletal dysplasia is a disease of osteochondrocytes with strong
clinical variability(Grannum and Hobbins, 1983; Liu, et al., 2019). Due
to their rarity, it is difficult to distinguish these types of diseases
during the fetal period(Yang, et al., 2019). The diagnosis of fetal
skeletal dysplasia can be done through prenatal ultrasound
evaluation(Yang, et al., 2019). Skeletal dysplasia often causes a
reduction in bust size and leads to lung dysplasia, so fetal skeletal
dysplasia is often fatal. However, due to the difficulty of fetal
ultrasound diagnosis, the severity of fetal skeletal dysplasia is
extremely difficult to assess(Tang, et al., 2020). The accuracy of
conventional ultrasound on fetal skeletal dysplasia is no more than
40%(Tang, et al., 2020). Misdiagnosis can lead to erroneous information
about the risk of relapse and delay optimal fetal management.
Using fetal imaging as a guide, a personalized prenatal genetic
examination strategy can be selected. Current options include chromosome
karyotype analysis, chromosome fluorescence in situ hybridization
experiments, chromosome microarray analysis, whole exome sequencing
etc(Petrovski, et al., 2019). According to the 2010 revision of the
Nosology and Classification of Genetic Skeletal Disorders, 456 diseases
were divided into 40 groups according to molecular, biochemical and
radiological standards(Warman, et al., 2011). Among them, 316
bone-related diseases are related to the mutation of one or more genes
in 226 different genes, which provides a basis for the molecular genetic
diagnosis of fetal skeletal development abnormalities(Warman, et al.,
2011). Two recent studies have shown that in the assessment of large
scale prospectively ascertained cohort of fetal with skeletal anomalies,
the diagnostic rates of skeletal dysplasia are 10/65 (15.4%)(Lord, et
al., 2019) and 8/34 (24%)(Petrovski, et al., 2019), respectively.
In our study, we analyzed 79 fetal
samples of skeletal dysplasia from the third affiliated hospital of
Zhengzhou University, China from August 2018 to April 2020, which had
undergone prenatal whole exome sequencing(WES). Our research aims to
explore the genetic types of fetal skeletal dysplasia in China, and
explore the correlation between results by WES and phenotype of skeletal
dysplasia in the fetal period by
ultrasound, with a view to providing a theoretical basis for early
implementation of birth defect intervention and reproductive risk
assessment.