Primary
lymphedema is clinically and genetically heterogeneous with germline mutations identified in approximately 20 primary
lymphedema genes. The lymphatic vessel endothelial
hyaluronan receptor-1 (LYVE-1) gene, also known as cell-surface retention sequence binding protein-1 (CRSBP-1), encodes the major
hyaluronan receptor in lymphatic endothelia and is one of the most specific lymphatic vessel markers. However, the role of this lymphatic endothelial specific
protein in the development of the lymphatic system and
lymphatic diseases remains unclear. Here, we report a missense mutation c.18C>G (p.S6R) in exon 1 within the N-terminal extension domain (outside the
hyaluronan binding region) of LYVE-1 in three generations of an inherited
lymphedema family with or without clinical symptoms. Lymphatic imaging revealed a partial, weak and delayed enhancement of tortuous lymph collectors in the distal part of the lymphedematous lower limb. Our findings revealed that LYVE-1/CRSBP-1 mutation in primary
lymphedema cases is connected with both structural and functional lymphatic defects.