Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways
Abstract
:1. Introduction
2. Results
2.1. Efficacy of the Current Genetic Tests
2.2. Study Cohort Characteristics
2.3. Molecular Pathways Involved in Primary Lymphedema
2.3.1. Diagnostic Gene Pathways
2.3.2. Candidate Gene Pathways
3. Discussion
3.1. Molecular Pathways Involved in Primary Lymphedema
3.1.1. VEGF-C/VEGFR-3 Pathway
3.1.2. HGF/MET Pathway
3.1.3. PI3K/AKT Pathway
3.1.4. RAS/MAPK Pathway
3.1.5. Rho/ROCK Pathway
3.1.6. Transcription Factors
3.2. Physiological Outcomes
3.2.1. Planar Cell Polarity and Lymphatic Valve Development
3.2.2. Lymph Pumping
3.2.3. Macrophage Activation and Lymphangiogenesis
3.3. Limitations and Future Perspectives
4. Materials and Methods
4.1. Genetic and Data Analysis
- Negative when no variants were found in the analyzed genes;
- Inconclusive when the detected variants could be causative of the disease, but their effect is uncertain;
- Positive when the detected variants were correlated with the disease.
4.2. Creation of Molecular Pathway Diagrams
- The gene is involved in the development of the lymphatic system in vivo;
- Gene mutations cause in vivo lymphatic defects;
- The gene participates in a molecular pathway that is important in lymphedema pathogenesis.
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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Characteristic | Case Subjects (n = 147) | |
---|---|---|
Age | Mean | 46 ± 18 |
Median | 47 ± 18 | |
Females/Males | 116/31 (79%/21%) | |
Period of onset | Congenital | 7 (5%) |
Childhood (1–10 years) | 26 (18%) | |
Youth (11–17 years) | 43 (29%) | |
Adult (>18 years) | 71 (48%) | |
Age of onset | Mean | 27 ± 18 |
Median | 25 ± 18 | |
Unknown | n = 39 | |
Sporadic | 79 (54%) | |
Familiarity | Familiar | 40 (27%) |
Unknown | 28 (19%) | |
Location | Lower limb | 49 (33%) |
Lower limbs | 77 (53%) | |
Upper limb | 6 (4%) | |
Lower and upper limbs | 12 (8%) |
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Bonetti, G.; Paolacci, S.; Samaja, M.; Maltese, P.E.; Michelini, S.; Michelini, S.; Michelini, S.; Ricci, M.; Cestari, M.; Dautaj, A.; et al. Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways. Int. J. Mol. Sci. 2022, 23, 7414. https://doi.org/10.3390/ijms23137414
Bonetti G, Paolacci S, Samaja M, Maltese PE, Michelini S, Michelini S, Michelini S, Ricci M, Cestari M, Dautaj A, et al. Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways. International Journal of Molecular Sciences. 2022; 23(13):7414. https://doi.org/10.3390/ijms23137414
Chicago/Turabian StyleBonetti, Gabriele, Stefano Paolacci, Michele Samaja, Paolo Enrico Maltese, Sandro Michelini, Serena Michelini, Silvia Michelini, Maurizio Ricci, Marina Cestari, Astrit Dautaj, and et al. 2022. "Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways" International Journal of Molecular Sciences 23, no. 13: 7414. https://doi.org/10.3390/ijms23137414