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.