Discovery of Pathogenic Variants Associated with Idiopathic Recurrent Pregnancy Loss Using Whole-Exome Sequencing
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Whole-Exome Sequencing
4.3. Annotation and Variant Filtering
4.4. Additional Annotation for Potential Variants
4.5. Validation
4.6. Replication of Patient and Control Samples
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Position | rsID | Gene | Transcript_ID | HGVS.c | HGVS.p | MAF frequency | Pathogenicity | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Replication Study | 1000 Genomes | KRGDB | KOREA1K | gnomAD Genomes_AF | VEST p-Value | VEST Missense | VEST Stop-Gain | CADD | SIFT | Polyphen2 | Detected Individual Count | ||||||
chr2 233274367 | rs575918099 | ALPG | NM_031313.3 | c.1384G>A | p.G462S | . | 0.0002 | 0.0038 | 0.0027 | . | 0.0170 | 0.775 | . | 24.4 | 0 | 1 | 1 |
chr2 238283646 | rs116238578 | COL6A3 | NM_057165.5 | c.2470G>A | p.V824M | 0.01327 | 0.0016 | 0.0013 | 0.0087 | 0.0003 | 0.0207 | 0.737 | . | 23.8 | 0 | 0.995 | 1 |
chr3 195488449 | rs200737893 | MUC4 | NM_138297.5 | c.1659G>A | p.W553 * | 0.00443 | 0.0004 | 0.0013 | 0.0027 | 0.0000 | 0.0060 | . | 0.634 | 51 | N/A | N/A | 1 |
chr10 115334164 | rs542838125 | HABP2 | NM_001177660.2 | c.145G>T | p.D49Y | 0.00443 | . | 0.0013 | 0.0005 | 0.0000 | 0.0150 | 0.799 | . | 32 | 0 | 0.987 | 1 |
chr16 16276686 | rs758166222 | ABCC6 | NM_001171.5 | c.2045A>T | p.K682M | . | . | 0.0010 | 0.0011 | . | 0.0145 | 0.805 | . | 24.5 | 0 | 1 | 2 |
chr16 16282707 | rs527236047 | ABCC6 | NM_001171.5 | c.1760C>G | p.S587C | 0.01327 | . | 0.0025 | 0.0022 | 0.0000 | 0.0398 | 0.613 | . | 24 | 0.03 | 0.979 | 1 |
chr17 34074883 | rs140842796 | GAS2L2 | NM_139285.4 | c.817C>T | p.R273C | 0.00885 | 0.0018 | 0.0013 | 0.0044 | 0.0004 | 0.0075 | 0.93 | . | 28.7 | 0 | 1 | 1 |
chr19 10897280 | rs763894364 | DNM2 | NM_001190716.2 | c.890G>A | p.R297H | . | 0.0002 | 0.0013 | 0.0005 | 0.0000 | 0.0129 | 0.827 | . | 28.6 | 0 | 0.942 | 1 |
chr20 48130848 | rs13306027 | PTGIS | NM_000961.4 | c.940G>T | p.E314 * | 0.00443 | . | 0.0013 | 0.0011 | 0.0000 | 0.0177 | . | 0.569 | 33 | N/A | N/A | 1 |
chr20 52789538 | rs114476330 | CYP24A1 | NM_001128915.2 | c.359G>A | p.R120H | . | 0.0002 | 0.0013 | 0.0033 | 0.0000 | 0.0159 | 0.788 | . | 32 | 0 | 1 | 1 |
Groups | Gene (rsID) (# of Patients/# of Controls) | |||
---|---|---|---|---|
Group 1 | ABCC6 (rs758166222) | DNM2 (rs763894364) | ALPG (rs575918099) | CYP24A1 (rs114476330) |
0/0 | 0/0 | 0/0 | 0/0 | |
Group 2 | MUC4 (rs200737893) | HABP2 (rs542838125) | GAS2L2 (rs140842796) | |
1/0 | 1/0 | 2/0 | ||
Group 3 | ABCC6 (rs527236047) | PTGIS (rs13306027) | ||
0/3 | 0/1 | |||
Group 4 | COL6A3 (rs116238578) | |||
2/1 |
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Lee, J.Y.; Moon, J.; Hu, H.-J.; Ryu, C.S.; Ko, E.J.; Ahn, E.H.; Kim, Y.R.; Kim, J.H.; Kim, N.K. Discovery of Pathogenic Variants Associated with Idiopathic Recurrent Pregnancy Loss Using Whole-Exome Sequencing. Int. J. Mol. Sci. 2024, 25, 5447. https://doi.org/10.3390/ijms25105447
Lee JY, Moon J, Hu H-J, Ryu CS, Ko EJ, Ahn EH, Kim YR, Kim JH, Kim NK. Discovery of Pathogenic Variants Associated with Idiopathic Recurrent Pregnancy Loss Using Whole-Exome Sequencing. International Journal of Molecular Sciences. 2024; 25(10):5447. https://doi.org/10.3390/ijms25105447
Chicago/Turabian StyleLee, Jeong Yong, JaeWoo Moon, Hae-Jin Hu, Chang Soo Ryu, Eun Ju Ko, Eun Hee Ahn, Young Ran Kim, Ji Hyang Kim, and Nam Keun Kim. 2024. "Discovery of Pathogenic Variants Associated with Idiopathic Recurrent Pregnancy Loss Using Whole-Exome Sequencing" International Journal of Molecular Sciences 25, no. 10: 5447. https://doi.org/10.3390/ijms25105447