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...
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MDPI AG
2024-02-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/14/3/253 |
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| author | Hu Tan Li Yu Jingsi Chen Xiaoyi Wang Fang He Lin Yu Lili Du Dunjin Chen |
| author_facet | Hu Tan Li Yu Jingsi Chen Xiaoyi Wang Fang He Lin Yu Lili Du Dunjin Chen |
| author_sort | Hu Tan |
| collection | DOAJ |
| description | 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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| spelling | doaj.art-9f340ff6e0934653a3d6067bea9e93742024-03-27T13:50:05ZengMDPI AGJournal of Personalized Medicine2075-44262024-02-0114325310.3390/jpm14030253Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and InvasionHu Tan0Li Yu1Jingsi Chen2Xiaoyi Wang3Fang He4Lin Yu5Lili Du6Dunjin Chen7Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaRare 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.https://www.mdpi.com/2075-4426/14/3/253early-onset preeclampsiaCCDC7rare variantstrophoblastmigration and invasion |
| spellingShingle | Hu Tan Li Yu Jingsi Chen Xiaoyi Wang Fang He Lin Yu Lili Du Dunjin Chen Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion Journal of Personalized Medicine early-onset preeclampsia CCDC7 rare variants trophoblast migration and invasion |
| title | Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion |
| title_full | Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion |
| title_fullStr | Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion |
| title_full_unstemmed | Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion |
| title_short | Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion |
| title_sort | rare mutations in ccdc7 contribute to early onset preeclampsia by inhibiting trophoblast migration and invasion |
| topic | early-onset preeclampsia CCDC7 rare variants trophoblast migration and invasion |
| url | https://www.mdpi.com/2075-4426/14/3/253 |
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