Can the Synergic Contribution of Multigenic Variants Explain the Clinical and Cellular Phenotypes of a Neurodevelopmental Disorder?
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Cell Cultures
2.3. Molecular Studies
2.3.1. Exome Sequencing, Variant Filtering and Prioritization, and CNV Calling
2.3.2. Transcript Analysis in Proband’s Blood and Fibroblasts
2.4. Test for Chromosome Instability Evaluation
2.5. Mitomycin C Sensitility Test
2.6. Complementation with Retroviral Vectors Expressing Functional FANCG
3. Results
3.1. Clinical Case
3.2. Exome Sequencing Analysis
3.3. Chromosome Instability Evaluation
3.4. Mitomycin C Sensitivity Test of Proband’s Cells
3.5. Reanalysis of ES Data Focusing on DNA Repair Genes
3.6. Complementation Studies with Retroviral Vectors Expressing Functional FANCG
4. Discussion
5. Final Remark
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | Group | Mean | Min | Max |
---|---|---|---|---|
Nr breaks/cell | FA | 8.96 | 1.30 | 23.90 |
Non-FA/control | 0.06 | 0.00 | 0.36 | |
% ab cells | FA | 85.15 | 12.60 | 100.00 |
Non-FA/control | 5.12 | 0.00 | 22.00 | |
Difference between FA and non-FA/control groups for the two parameters: number of breaks per cell (Nr breaks/cell) and percentage of aberrant cell, i.e., cells with breaks (% ab cells). |
DEB-Induced CI | DEB Concentration: 0.05 µg/mL (Diagnostic Discriminative Parameters to Compare with Reference Values in Table 1) | DEB Concentration 0.1 µg/mL | ||
---|---|---|---|---|
% ab Cells | Nr Breaks/Cell | % ab Cells | Nr Breaks/Cell | |
Proband | 34 | 0.54 | 76 | 1.88 |
Mother’s Proband | 4 | 0.06 | 5 | 0.05 |
Father’s Proband | 1 | 0.01 | 3 | 0.03 |
Healthy Donor (Negative Control) | 3 | 0.04 | 2 | 0.02 |
FA Patient (Positive Control) | 89 | 5.36 | No Metaphases |
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Maia, N.; Nabais Sá, M.J.; Oliveira, C.; Santos, F.; Soares, C.A.; Prior, C.; Tkachenko, N.; Santos, R.; de Brouwer, A.P.M.; Jacome, A.; et al. Can the Synergic Contribution of Multigenic Variants Explain the Clinical and Cellular Phenotypes of a Neurodevelopmental Disorder? Genes 2022, 13, 78. https://doi.org/10.3390/genes13010078
Maia N, Nabais Sá MJ, Oliveira C, Santos F, Soares CA, Prior C, Tkachenko N, Santos R, de Brouwer APM, Jacome A, et al. Can the Synergic Contribution of Multigenic Variants Explain the Clinical and Cellular Phenotypes of a Neurodevelopmental Disorder? Genes. 2022; 13(1):78. https://doi.org/10.3390/genes13010078
Chicago/Turabian StyleMaia, Nuno, Maria João Nabais Sá, Cláudia Oliveira, Flávia Santos, Célia Azevedo Soares, Catarina Prior, Nataliya Tkachenko, Rosário Santos, Arjan P. M. de Brouwer, Ariana Jacome, and et al. 2022. "Can the Synergic Contribution of Multigenic Variants Explain the Clinical and Cellular Phenotypes of a Neurodevelopmental Disorder?" Genes 13, no. 1: 78. https://doi.org/10.3390/genes13010078
APA StyleMaia, N., Nabais Sá, M. J., Oliveira, C., Santos, F., Soares, C. A., Prior, C., Tkachenko, N., Santos, R., de Brouwer, A. P. M., Jacome, A., Porto, B., & Jorge, P. (2022). Can the Synergic Contribution of Multigenic Variants Explain the Clinical and Cellular Phenotypes of a Neurodevelopmental Disorder? Genes, 13(1), 78. https://doi.org/10.3390/genes13010078