Possible Role of the <i>RORC</i> Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants
Sandro Michelini, Maurizio Ricci, Roberta Serrani, Liborio Stuppia, Tommaso Beccari, Dominika Vešelényiová, Sercan Kenanoğlu, Shila Barati, Danjela Kurti, Mirko Baglivo, Syed Hussain Basha, Juraj Krajčovič, Munis Dündar, Matteo Bertelli
Abstract
Background: RAR-related Orphan Receptor C (RORC) is a DNA-binding transcription factor and the key transcription factor responsible for differentiation of T helper 17 cells. The RORC gene plays a role in lymphoid organogenesis, thymopoiesis, and lymph node organogenesis. The aim of our study was to determine the possible role of RORC in the development of lymphatic system malformations by combining data from the scientific literature and next-generation sequencing of RORC in lymphedema patients negative for known causative genes. Methods and Results: We sequenced RORC in 235 lymphedema patients negative for known lymphedema-associated genes. We found two probands carrying nonsense RORC variants. Conclusions: We show that RORC is important for normal function of the lymphatic system and that a rare variant with a possible causative effect may imply predisposition for lymphedema.