Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion
Abstract
:1. Introduction
2. Methods
2.1. Patients
2.2. Whole-Exome Sequencing and Data Analysis
2.3. Cell Culture
2.4. Generation of Stable CCDC7 Knockdown Cell Lines
2.5. RNA Extraction and Quantitative Real-Time Polymerase Chain Reaction
2.6. Protein Extraction and Western Blot Analysis
2.7. Immunofluorescence
2.8. Wound-Healing Assay
2.9. Transwell Invasion Assay
2.10. Statistical Analysis
3. Results
3.1. Clinical Features and Rare Variants of CCDC7 Detected in Two EOPE Families
3.2. Whole-Exome Sequencing Identified Rare Variants in CCDC7 in Familial Preeclampsia
3.3. CCDC7 Spatial and Temporal Expression Patterns in the Human Placenta
3.4. Expression and Distribution of Rare CCDC7 Variants in the Placenta
3.5. Effects of CCDC7 on JEG-3 Cell Migration and Invasion
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CCDC | Coiled-coil domain-containing |
CTBs | cytotrophoblast cells |
EOPE | Early-onset preeclampsia |
GWAS | Genome-wide association studies |
LOPE | Late-onset preeclampsia |
MMPs | Matrix metalloproteinases |
PVDF | Polyvinylidene fluoride |
qRT-PCR | Quantitative real-time polymerase chain reaction |
SDS-PAGE | Sodium dodecyl sulfate-polyacrylamide gel-electrophoresis |
STBs | Syncytiotrophoblasts |
WES | Whole-exome sequencing |
WGS | Whole-genome sequencing |
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Family No. | A | A | A | B | B | |
---|---|---|---|---|---|---|
Mother | II-2 | II-6 | II-8 | I-2 | II-2 | |
Onset time at pregnancy (Week) | 24+1 | 27+0 | 32+0 | NA | 32+1 | |
Gestational age at delivery (Week) | 34+4 | 27+4 | 32+0 | 36+4 | 36+4 | |
High blood pressure * | Yes | Yes | Yes | Yes | Yes | |
Proteinuria * | Yes | Yes | Yes | Yes | Yes | |
Impaired liver function * | No | No | No | NA | No | |
Renal insufficiency * | No | No | No | NA | No | |
Thrombocytopenia * | No | No | No | NA | No | |
Pulmonary edema * | No | No | No | NA | No | |
Headache and/or visual symptoms * | No | No | Yes | NA | No | |
Offspring | III-1 | III-8 | III-9 | II-2 | III-2 | IIII-3 |
Sex | Female | Female | Female | Female | Male | Female |
Birth weight (g) | 2100 | 750 | 1500 | NA | 2340 | 2470 |
Apgar score 1 min | 10′ | 8′ | 4′ | NA | 10′ | 10′ |
Apgar score 5 min | 10′ | 10′ | 7′ | NA | 10′ | 10′ |
Apgar score 10 min | 10′ | 10′ | 10′ | NA | 10′ | 10′ |
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Tan, H.; Yu, L.; Chen, J.; Wang, X.; He, F.; Yu, L.; Du, L.; Chen, D. Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion. J. Pers. Med. 2024, 14, 253. https://doi.org/10.3390/jpm14030253
Tan H, Yu L, Chen J, Wang X, He F, Yu L, Du L, Chen D. Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion. Journal of Personalized Medicine. 2024; 14(3):253. https://doi.org/10.3390/jpm14030253
Chicago/Turabian StyleTan, Hu, Li Yu, Jingsi Chen, Xiaoyi Wang, Fang He, Lin Yu, Lili Du, and Dunjin Chen. 2024. "Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion" Journal of Personalized Medicine 14, no. 3: 253. https://doi.org/10.3390/jpm14030253