GENETIC VARIANTS IN THE TRANSCRIPTION FACTOR NETWORK: THE IMPACT OF FOXC1, NOTCH1, RORC, FOXC2 AND SOX18 IN PRIMARY LYMPHEDEMA
Abstract
Lymphedema is a chronic inflammatory disease caused by defective lymphatic system function or development that proceeds in abnormal fluid drainage and edema of the peripheral tissues. This retrospective study evaluates the potential role of transcription factors in the development of primary lymphedema. We analyzed 408 Italian primary lymphedema patients for pathogenic variants in genes related to the transcription factor network. Eighteen likely pathogenic genetic variants were identified in 5 genes - FOXC1, FOXC2, NOTCH1, RORC, and SOX18 - most of which have not been previously reported in the literature. Although majority of these genetic variants resulted in premature termination of the proteins, a single missense variant was identified in FOXC2 and analyzed in this study using molecular modeling approaches to evaluate its structural changes. These results suggested possible deleterious effects of the analyzed variant and supported its potential pathogenicity. Our findings provide additional evidence that associates variants in transcription factors to the onset of lymphedema and support the addition of the candidate genes FOXC1, NOTCH1, and RORC in primary lymphedema diagnostic practice.
Keywords: Primary lymphedema, transcription factors, Regulatory networks, Molecular modeling, FOXC2
How to Cite:
Gelanová, V., Veselenyiova, D., Kozáčiková, R., Belanová, I., Bonetti, G., Kaftalli, J., Ferrari, L., Macchia, A., Medori, M., Dhuli, K., Guerri, G., Miertus, S., Miertus, J., Ricci, M., Cestari, M., Amato, B., Boccardo, F., Michelini, S., Michelini, S., Cecchin, S., Lee, S., Suppiramaniam, V., Bertelli, M. & Michelini, S., (2025) “GENETIC VARIANTS IN THE TRANSCRIPTION FACTOR NETWORK: THE IMPACT OF FOXC1, NOTCH1, RORC, FOXC2 AND SOX18 IN PRIMARY LYMPHEDEMA”, Lymphology 58(3). doi: https://doi.org/10.2458/lymph.10277
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