ArticleOncotarget2016
FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- FOXC2 represses NFAT1-dependent transcription through a DNA-facilitated protein-protein interaction.Nucleic acids research · 2026Article
- Cancer and lymphatic marker FOXC2 drives wound healing and fibrotic tissue formation.Frontiers in physiology · 2024Article
- Genomic analysis and prediction of genomic values for distichiasis in Staffordshire bull terriers.Canine medicine and genetics · 2023Article
- Haploinsufficiencies of FOXF1, FOXC2 and FOXL1 genes originated from deleted 16q24.1q24.2 fragment related with alveolar capillary dysplasia with misalignment of pulmonary veins and lymphedema-distichiasis syndrome: relationship to phenotype.Molecular cytogenetics · 2022Article
- Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways.International journal of molecular sciences · 2022Article
- Microdeletion of 16q24.1-q24.2-A unique etiology of Lymphedema-Distichiasis syndrome and neurodevelopmental disorder.American journal of medical genetics. Part A · 2022Article
- Current Understanding of Pathological Mechanisms of Lymphedema.Advances in wound care · 2022Review
- Digenic Inheritance of a FOXC2 Mutation and Two PIEZO1 Mutations Underlies Congenital Lymphedema in a Multigeneration Family.The American journal of medicine · 2022Article
- Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation.Frontiers in physiology · 2022Review
- Insights into the pathogenicity of missense variants in the forkhead domain of FOX proteins underlying Mendelian disorders.Human genetics · 2021Article
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- The Impact of Estrogen Receptor in Arterial and Lymphatic Vascular Diseases.International journal of molecular sciences · 2020Review
- The FKH domain in FOXP3 mRNA frequently contains mutations in hepatocellular carcinoma that influence the subcellular localization and functions of FOXP3.The Journal of biological chemistry · 2020Article
- Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem.BMC medical genomics · 2019Article
- Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis.Nature reviews. Rheumatology · 2018Review
- FOXC1, the new player in the cancer sandbox.Oncotarget · 2018Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dominant mutations in the FOXC2 gene cause a form of lymphedema primarily of the limbs that usually develops at or after puberty. In 90-95% of patients, lymphedema is accompanied by distichiasis. FOXC2 is a member of the forkhead/winged-helix family of transcription factors and plays essential roles in different developmental pathways and physiological processes. We previously described six unrelated families with primary lymphedema-distichiasis in which patients showed different FOXC2 mutations located outside of the forkhead domain. Of those, four were missense mutations, one a frameshift mutation, and the last a stop mutation. To assess their pathogenic potential, we have now examined the subcellular localization and the transactivation activity of the mutated FOXC2 proteins. All six FOXC2 mutant proteins were able to localize into the nucleus; however, the frameshift truncated protein appeared to be sequestered into nuclear aggregates. A reduction in the ability to activate FOXC1/FOXC2 response elements was detected in 50% of mutations, while the remaining ones caused an increase of protein transactivation activity. Our data reveal that either a complete loss or a significant gain of FOXC2 function can cause a perturbation of lymphatic vessel formation leading to lymphedema.
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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.