Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways

Lymphedema is a chronic inflammatory disorder caused by ineffective fluid uptake by the lymphatic system, with effects mainly on the lower limbs. Lymphedema is either primary, when caused by genetic mutations, or secondary, when it follows injury, infection, or surgery. In this study, we aim to assess to what extent the current genetic tests detect genetic variants of lymphedema, and to identify the major molecular pathways that underlie this rather unknown disease. We recruited 147 individuals with a clinical diagnosis of primary lymphedema and used established genetic tests on their blood or saliva specimens. Only 11 of these were positive, while other probands were either negative (63) or inconclusive (73). The low efficacy of such tests calls for greater insight into the underlying mechanisms to increase accuracy. For this purpose, we built a molecular pathways diagram based on a literature analysis (OMIM, Kegg, PubMed, Scopus) of candidate and diagnostic genes. The PI3K/AKT and the RAS/MAPK pathways emerged as primary candidates responsible for lymphedema diagnosis, while the Rho/ROCK pathway appeared less critical. The results of this study suggest the most important pathways involved in the pathogenesis of lymphedema, and outline the most promising diagnostic and candidate genes to diagnose this disease. View Full-Text

Keywords: lymphedema; molecular pathways; genetic screening; diagnostic genes; candidate genes; PI3K/AKT; RAS/MAPK; Rho/ROCK

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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.; Medori, M.C.; Bertelli, M. 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

AMA Style

Bonetti G, Paolacci S, Samaja M, Maltese PE, Michelini S, Michelini S, Michelini S, Ricci M, Cestari M, Dautaj A, Medori MC, Bertelli M. 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 Style

Bonetti, Gabriele, Stefano Paolacci, Michele Samaja, Paolo Enrico Maltese, Sandro Michelini, Serena Michelini, Silvia Michelini, Maurizio Ricci, Marina Cestari, Astrit Dautaj, Maria Chiara Medori, and Matteo Bertelli. 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

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Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways

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