Targeted Next Generation Sequencing unravels loss-of-function mutations in two lymphangiogenic factors in primary lymphedema patients
(2018)
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- Abstract
- Primary lymphedema (PLE) is an accumulation of lymph characterized by swelling of parts of the body, that can be transmitted from generation to generation. But at least 60% of patients were not genetically explained. In a cohort of 542 patients, 66 genes were screened. Causative mutations in 14 known genes explained about 40% of inherited PLE whom novel ones in “unappreciated” genes encoding growth factors, VEGFC and HGF. For these last ones, in vitro studies revealed loss-of-function responsible of PLE by haploinsufficiency or hypomorphic alleles. Reduced activity of the c-MET/PI3K/AKT pathway due to HGF deficiency underscores the crucial role of this pathway in the disease. This thesis contributed to determine the origin of lymphedema of a larger number of patients. Recognition of causative mutations among variants of uncertain significance is still useful to explain more patients but other candidate genes are likely to be discovered by whole exome sequencing.
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Fastre, E. (2018). Targeted Next Generation Sequencing unravels loss-of-function mutations in two lymphangiogenic factors in primary lymphedema patients. https://hdl.handle.net/2078.5/27997