Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic TREX1 Missense Variants Affecting the Catalytic Core
Abstract
:1. Introduction
2. Results
2.1. Clinical and Neuroradiological Features of Patients
2.1.1. Patient A
2.1.2. Patient B
2.2. Genetic Analysis Findings
2.3. Peripheral Blood Type I Interferon Activity
2.4. Exonuclease Activities of Mutant Enzymes
3. Discussion
4. Material & Methods
4.1. Genetic Analysis
4.2. Bioinformatic Analysis of NGS-Panels Genetic Data
4.3. Peripheral Blood Type I Interferon Signature
4.4. Generation of Wild-Type and Mutant TREX1 Plasmids
4.5. Overexpression and Purification of Recombinant TREX1 Enzymes
4.6. Fluorescence-Based dsDNA Exonuclease Assay
4.7. Fluorescence-Based ssDNA Exonuclease Assay
4.8. Quantification of Fluorescence-Based Data
4.9. Agarose Gel dsDNA Assay
4.10. Quantification of Agarose Gels
4.11. Polyacrylamide Gel ssDNA Assay
4.12. Quantification of Polyacrylamide Gels
4.13. Observation-Theory Comparisons for Exonuclease Activities
4.14. Modeling of Human TREX1 Enzyme Structure
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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pt | Variants Description | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GENE | cDNA Change | Protein Change | dbSNP | zig | seg | Varsome | Clinvar | CADD | MAF * | Hom # | Polyphen | SIFT | |
A | TREX1 | c.407C>T | p.A136V | rs1560112354 | het | pat | LP | - | 28 | 0.8 × 10−5 | 0 | 0.448 | 0.01 |
B | TREX1 | c.520A>G | p.R174G | rs759481016 | het | NA | LP | - | 27 | 0.17 × 10−4 | 0 | 0.623 | 0.02 |
B | RANBP2 | c.8591G>T | p.G2864V | rs765893725 | het | NA | VUS | - | 28 | 0.289 × 10−4 | 0 | 0.999 | 0 |
B | TBXAS1 | c.319A>G | p.N107D | rs771726219 | het | NA | VUS | - | 26 | 0.176 × 10−4 | 0 | 0.986 | 0.08 |
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Amico, G.; Hemphill, W.O.; Severino, M.; Moratti, C.; Pascarella, R.; Bertamino, M.; Napoli, F.; Volpi, S.; Rosamilia, F.; Signa, S.; et al. Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic TREX1 Missense Variants Affecting the Catalytic Core. Genes 2022, 13, 1179. https://doi.org/10.3390/genes13071179
Amico G, Hemphill WO, Severino M, Moratti C, Pascarella R, Bertamino M, Napoli F, Volpi S, Rosamilia F, Signa S, et al. Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic TREX1 Missense Variants Affecting the Catalytic Core. Genes. 2022; 13(7):1179. https://doi.org/10.3390/genes13071179
Chicago/Turabian StyleAmico, Giulia, Wayne O. Hemphill, Mariasavina Severino, Claudio Moratti, Rosario Pascarella, Marta Bertamino, Flavia Napoli, Stefano Volpi, Francesca Rosamilia, Sara Signa, and et al. 2022. "Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic TREX1 Missense Variants Affecting the Catalytic Core" Genes 13, no. 7: 1179. https://doi.org/10.3390/genes13071179
APA StyleAmico, G., Hemphill, W. O., Severino, M., Moratti, C., Pascarella, R., Bertamino, M., Napoli, F., Volpi, S., Rosamilia, F., Signa, S., Perrino, F., Zedde, M., Ceccherini, I., & on behalf of the Gaslini Stroke Study Group. (2022). Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic TREX1 Missense Variants Affecting the Catalytic Core. Genes, 13(7), 1179. https://doi.org/10.3390/genes13071179