A LYVE-1/CRSBP-1 Mutation in Inherited Primary Lymphedema

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.