ArticleAmerican journal of human genetics2010
GJC2 missense mutations cause human lymphedema.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 175 citations in OpenAlex.
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Novel GJC2 and OBSCN variants co-segregating in a Chinese primary lymphedema pedigree.Orphanet journal of rare diseases · 2026Article
- Decreased Kinase Activity of the VEGFR3 Variant c.3175G>C Associated with Primary Lymphedema.Current issues in molecular biology · 2026Article
- Transcriptomics- and 3D imaging-based characterization of the lymphatic vasculature in human skin.The Journal of experimental medicine · 2026Article
- Review
- Hierarchical Requirement for Endothelial Cell Connexins Cx37, Cx47, Cx43, and Cx45 in Lymphatic Valve Function.Function (Oxford, England) · 2025Article
- Molecular dynamics simulation of GJC2 mutants reveal pathogenic mechanisms of PMLD1 and SPG44.The Journal of general physiology · 2025Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
- Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.JCI insight · 2024Article
- Pathogenic variants in HGF give rise to childhood-to-late onset primary lymphoedema by loss of function.Human molecular genetics · 2024Article
- Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models.The Journal of clinical investigation · 2024Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction.Frontiers in immunology · 2024Article
- Protective role of Pannexin1 in lymphatic endothelial cells in the progression of atherosclerosis in female mice.PloS one · 2024Article
- Description of Phenotypic Heterogeneity in aMolecular syndromology · 2023Article
- Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.Clinical science (London, England : 1979) · 2023Review
- [Genetics, diagnostics and clinical presentation of primary lymphoedema].Dermatologie (Heidelberg, Germany) · 2023Review
- The Enigmas of Lymphatic Muscle Cells: Where Do They Come From, How Are They Maintained, and Can They Regenerate?Current rheumatology reviews · 2023Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Lymphedema is the clinical manifestation of defects in lymphatic structure or function. Mutations identified in genes regulating lymphatic development result in inherited lymphedema. No mutations have yet been identified in genes mediating lymphatic function that result in inherited lymphedema. Survey microarray studies comparing lymphatic and blood endothelial cells identified expression of several connexins in lymphatic endothelial cells. Additionally, gap junctions are implicated in maintaining lymphatic flow. By sequencing GJA1, GJA4, and GJC2 in a group of families with dominantly inherited lymphedema, we identified six probands with unique missense mutations in GJC2 (encoding connexin [Cx] 47). Two larger families cosegregate lymphedema and GJC2 mutation (LOD score = 6.5). We hypothesize that missense mutations in GJC2 alter gap junction function and disrupt lymphatic flow. Until now, GJC2 mutations were only thought to cause dysmyelination, with primary expression of Cx47 limited to the central nervous system. The identification of GJC2 mutations as a cause of primary lymphedema raises the possibility of novel gap-junction-modifying agents as potential therapy for some forms of lymphedema.
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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.