ArticleThe Journal of clinical investigation2016
EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- A Framework for Bioinformatic Reporting in Prenatal Sequencing: Insights From a Systematic Review.Prenatal diagnosis · 2026Pooled it
- Global Recommendations for the Use of Diagnostic Genomic Sequencing in the Prenatal Setting on Behalf of the ESHG and ISPD.Prenatal diagnosis · 2026Article
- Global recommendations for the use of diagnostic genomic sequencing in the prenatal setting on behalf of the ESHG and ISPD.European journal of human genetics : EJHG · 2026Article
- [Cystic lymphangioma of the penis in an adult: A case report].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- Insights into KIF11 pathogenesis in microcephaly-lymphedema-chorioretinopathy syndrome from a lymphatic perspective.JCI insight · 2026Article
- m5C and m6A cooperatively stabilize EPHB4 to drive lymphatic metastasis in gastric cancer.Frontiers in genetics · 2026Article
- Insights Into Congenital Lymphatic Anomalies Underlying Fetal Effusions.Prenatal diagnosis · 2026Article
- Impaired lymphatic drainage in a child with hydrops fetalis and a novel variant in the PROX1 gene: case report and review of literature.Frontiers in cardiovascular medicine · 2026Article
- Further characterisation of immortalised human lymphatic endothelial cells to explore their transcriptomic profile and VEGFC response.Scientific reports · 2025Article
- Refractory Diarrhea Related to EPHB4 Mutation in a Patient With Capillary Malformation-Arteriovenous Type 2 Syndrome.ACG case reports journal · 2025Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Arteriovenous cerebral high-flow shunts: genetic analysis of patients from a pediatric tertiary care center.Frontiers in genetics · 2025Article
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- Lymphatic System Development and Function.Current cardiology reports · 2024Review
- Novel postzygoticClinical case reports · 2024Article
- Specific Circular RNA Signature of Endothelial Cells: Potential Implications in Vascular Pathophysiology.International journal of molecular sciences · 2024Article
- An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves.bioRxiv : the preprint server for biology · 2023Article
- Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.Nature communications · 2023Article
- Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal transduction and targeted therapy · 2023Article
- Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.Journal of vascular anomalies · 2023Review
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 4 countries.
Funding
Abstract
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 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.