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

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.