| Summary: | 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 <i>CCDC7</i>, 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 <i>CCDC7</i> in human placental villi and the effects of <i>CCDC7</i> on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of <i>CCDC7</i> in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The <i>CCDC7</i> p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of <i>CCDC7</i> suppressed the migration and invasion of JEG-3 cells. In conclusion, <i>CCDC7</i> 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.
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