Prenatal diagnosis of skeletal dysplasias using whole exome sequencing in China

•We explored the potential for a molecular diagnosis of prenatalskeletal dysplasias using WES in China.•We got an 80% diagnosis rate higher than most previous studies, because we have used WES and US to prenatal diagnosis.•Greenberg skeletal dysplasia is a very rare, we reported one fetus casecaused by LBR mutations.•Our research may enrich the mutation spectrum of LBR, COL1A2,COL2A1 and FGFR3 genes in the Chinese population and improveunderstanding the pathogenesis of skeletal dysplasias. Skeletal dysplasias account for nearly 10% of fetal structural malformations detected by ultrasonography. This clinically heterogeneous group of genetic anomaly includes at least 461 genetic skeletal disorders with extreme clinical, phenotypic, and genetic heterogeneities, thus, significantly complicates accurate diagnosis. Researches have used whole exome sequencing (WES) for prenatal molecular diagnoses of skeletal dysplasias, however, data are still limited. DNA extracted from umbilical cord blood or amniocytes from fetuses suspected of skeletal dysplasias based on ultrasound evaluations were analyzed by WES. Blood samples were taken from the parents of the positive fetuses for co-segregation analysis using Sanger sequencing. Definitive molecular diagnosis was made in 6/8 (75%) cases, comprised of 5 de novo disease-causing changes in 3 genes (FGFR3, COL2A1, and COL1A2) and one proband with a biallelic deficiency for Lamin B Receptor(LBR),and including 3 novel variants. All fetuses had no detectable copy number variation (CNV) from sequencing results. Our study suggests that WES is an efficient approach for prenatal diagnosis of fetuses suspected of skeletal abnormalities and contributes to parental genetics counseling and pregnancy management.