Revencu, NicoleVikkula, MiikkaMengeot, LauraLauraMengeot2025-02-042025-02-042018https://dial-mem.test.bib.ucl.ac.be/handle/123456789/22433Lymphedema is a common disabling condition and is also the most frequent lymphatic anomaly. It is characterized by a chronic tissue swelling mostly in the limbs. Lymphedema can be primary or secondary (acquired): the primary forms result from inadequate development or function of the lymphatic system. Currently, germline mutations have been identified in 28 genes. However these only explain about 40% of familial forms and 12% of sporadic forms of primary lymphedema hinting at the responsibility of other genes. The hepatocyte growth factor (HGF) was suggested as potential new causal gene for primary lymphedema. Indeed, it had been recognized as strong promotor of lymphangiogenesis by various studies. An association between HGF and primary lymphedema had been reported in the literature but only in 2 studies. Considering the paucity of information available, there was a need to clarify the contribution of HGF in the etiopathogenesis of lymphedema. Thus, the host laboratory screened a cohort of patients for mutation and identified 12 HGF variants in 11 patients. An accurate description of the phenotype associated to HGF mutation was lacking, as clinical features were only summarily mentioned in the 2 studies reporting an association between primary lymphedema and HGF. A major part of our study was thus consecrated to the innovative project of characterizing HGF-phenotype. To accomplish this task, patient’s clinical features were analyzed in detailed using a specific official lymphedema questionnaire as well as the medical records when available. We observed that HGF mutations were associated to an isolated lower limbs lymphedema of late onset, the severity of which varied depending on the level of HGF loss. This study permitted an accurate delineation of the phenotypic spectrum likely to manifest in patients with HGF mutation, positioning HGF in the clinical differential diagnosis of the heterogeneous group of primary lymphedema, as well as a demonstration of the existence of a correlation between the phenotype and the genotype. The final part of our study was devoted to the analysis of 7 cases of mutated primary lymphedema followed at Cliniques Universitaires Saint Luc, Brussels, illustrating some of the well-known genes responsible for primary lymphedema. The objective was to review the literature and to emphasize some key messages.Primary lymphedemaHGFtext::thesis::master thesisthesis:13430