Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion.

Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in , c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of in human placental villi and the effects of on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of suppressed the migration and invasion of JEG-3 cells. In conclusion, is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.