Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (
Silvia Martin-Almedina, Ines Martinez-Corral, Rita Holdhus, Andres Vicente, Elisavet Fotiou, Shin Lin, Kjell Petersen, Michael A. Simpson, Alexander Hoischen, Christian Gilissen, Heather Jeffery, Giles Atton, Christina Karapouliou, Glen Brice, Kristiana Gordon, John W. Wiseman, Marianne Wedin, Stanley G. Rockson, Steve Jeffery, Peter S. Mortimer, Michael P. Snyder, Siren Berland, Sahar Mansour, Taija Makinen, Pia Ostergaard
Effect of p.Arg739Glu and p.Ile782Ser mutations on EPHB4 tyrosine phosphorylation in HEK293T cells.