A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy
Abstract
:1. Introduction
2. Experimental Section
2.1. Ethics Statement
2.2. Subject and Ophthalmologic Examination
2.3. Sanger Sequencing of OVOL2, COL8A2, ZEB1, SLC4A11 and GRHL2
2.4. Array-Comparative Genomic Hybridization (CGH)
2.5. Haplotype Analysis
2.6. Whole Exome Sequencing
2.7. Modeling of ZNF143 p.Asp313His
2.8. In Vitro Functional Studies of ZNF143 p.Asp313His
2.8.1. Isolation and Culture of Human Corneal Endothelial Cells (hCECs)
2.8.2. siRNA-Mediated Silencing of Human ZNF143
2.8.3. Transfection of Human ZNF143 (Wild Type and Mutant)
2.8.4. Gene Expression Analysis
2.8.5. Immunoblotting
2.9. Immunohistochemical Staining
3. Results
3.1. Patients Characteristics
3.2. ZNF143 c.937G>C p.(Asp313His) Mutation Was Identified as a New Candidate for Endothelial CD
3.3. Three-Dimensional Modeling of ZNF143 p.Asp313His
3.4. In Vitro Functional Studies of ZNF143 c.937G>C p.Asp313His
3.5. Network Analysis Reveals Activation of Epithelialization and Proinflammatory Signals
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Chr | Gene | Annotation | SIFT (Score) | PolyPhen (Score) | Mutation Taster | Evola | dbSNP | GnomAD Exomes | KRG DB | ACMG Criteria | ACMG Classification |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | TXNIP | NM_006472:exon5: c.A805G:p.I269V | deleterious 0.04 | probably damaging 0.996 | disease causing | conserved (12/12) | - | 0.000003977 | - | BS2, PP3, PP4 | VUS |
2 | EPC2 | NM_015630:exon8: c.G1208A:p.R403Q | deleterious 0.01 | benign 0.383 | disease causing | conserved (11/15) | rs761809638 | 0.00008181 | - | BS2, PP4 | VUS |
9 | KCNV2 | NM_133497:exon1: c.G217C:p.E73Q | tolerated 0.08 | benign 0.005 | polymorphism | conserved (12/13) | rs752013234 | 0.00001593 | - | BS2, PP4 | VUS |
9 | NUTM2F | NM_017561:exon7: c.C1766G:p.A589G | deleterious 0.05 | probably damaging 0.985 | polymorphism | no data | rs201719890 | 0.04351 | 0.2363 | BA1, PP4 | Benign (I) |
9 | AOPEP | NM_001193329: exon10:c.A1960G:p.S654G | benign 0.018 | polymorphism | conserved (7/15) | - | - | - | PM2, PP4 | VUS | |
9 | TNC | NM_002160:exon3: c.C1063T:p.R355W | deleterious 0 | possibly damaging 0.677 | disease causing | conserved (8/15) | rs779621288 | 0.00001195 | - | BS2, PP3, PP4 | VUS |
9 | RABGAP1 | NM_012197:exon10: c.G1221A:p.M407I | tolerated 0.07 | benign 0.015 | disease causing | N/A | rs769879519 | 0.000008117 | - | BS2, PP4 | VUS |
11 | ZNF143 | NM_003442:exon10: c.G937C:p.D313H | deleterious 0.02 | probably damaging 0.949 | disease causing | conserved (15/15) | - | - | - | PM2, PP3, PP4 | Likely pathogenic (II) |
13 | ERICH6B | NM_182542:exon3: c.C302A:p.A101E | Tolerated 1 | unknown | polymorphism | no data | - | - | - | PM2, PP4 | VUS |
19 | MZF1 | NM_003422:exon6: c.G1952A:p.R651Q | deleterious 0.04 | probably damaging 0.994 | polymorphism | conserved (9/9) | rs201221836 | 0.0002058 | 0.0105 | BS2, PP4 | VUS |
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Kim, Y.; You, H.J.; Park, S.H.; Kim, M.S.; Chae, H.; Park, J.; Jekarl, D.W.; Kim, J.; Kwon, A.; Choi, H.; et al. A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy. J. Clin. Med. 2019, 8, 1174. https://doi.org/10.3390/jcm8081174
Kim Y, You HJ, Park SH, Kim MS, Chae H, Park J, Jekarl DW, Kim J, Kwon A, Choi H, et al. A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy. Journal of Clinical Medicine. 2019; 8(8):1174. https://doi.org/10.3390/jcm8081174
Chicago/Turabian StyleKim, Yonggoo, Hye Jin You, Shin Hae Park, Man Soo Kim, Hyojin Chae, Joonhong Park, Dong Wook Jekarl, Jiyeon Kim, Ahlm Kwon, Hayoung Choi, and et al. 2019. "A Mutation in ZNF143 as a Novel Candidate Gene for Endothelial Corneal Dystrophy" Journal of Clinical Medicine 8, no. 8: 1174. https://doi.org/10.3390/jcm8081174