ArticleHuman molecular genetics2021
A novel somatic mutation in GNB2 provides new insights to the pathogenesis of Sturge-Weber syndrome.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 63 citations in OpenAlex.
- Familial p.(Ala73Thr) Variant inClinical case reports · 2026Article
- In Vitro Models of Sturge-Weber Syndrome: Strengths, Limitations, and Future Goals.International journal of molecular sciences · 2026Review
- Clinical Validation of a Fast MRI Method to Evaluate Brain Vascular and Parenchymal Abnormalities in Sturge-Weber Syndrome.Journal of magnetic resonance imaging : JMRI · 2026Observational
- Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in Gαq-R183Q-driven capillary malformations.Angiogenesis · 2026Article
- Biomarker development in Sturge-Weber syndrome.Journal of neurodevelopmental disorders · 2025Review
- Sturge Weber syndrome in a multinational pediatric cohort: a systematic analysis of different types.Orphanet journal of rare diseases · 2025Observational
- Transcriptomic Profiling Unveils EDN3Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sturge-Weber syndrome secondary glaucoma: From Pathogenesis to Treatment.Eye and vision (London, England) · 2025Review
- Somatic Mosaicism in Brain Disorders.Annual review of pathology · 2025Review
- YAP/TAZ-associated cell signaling - at the crossroads of cancer and neurodevelopmental disorders.Frontiers in cell and developmental biology · 2025Review
- A Review of Sturge-Weber Syndrome Brain Involvement, Cannabidiol Treatment and Molecular Pathways.Molecules (Basel, Switzerland) · 2024Review
- Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations.Angiogenesis · 2024Article
- Similarities and differences between brain and skinbioRxiv : the preprint server for biology · 2024Article
- Assessment of gene-disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA.Orphanet journal of rare diseases · 2024Article
- Capillary malformations.The Journal of clinical investigation · 2024Review
- GNAQ/GNA11 Mosaicism Causes Aberrant Calcium Signaling Susceptible to Targeted Therapeutics.The Journal of investigative dermatology · 2024Article
- MRC1 and LYVE1 expressing macrophages in vascular beds of GNAQ p.R183Q driven capillary malformations in Sturge Weber syndrome.Acta neuropathologica communications · 2024Article
- Sturge-Weber syndrome: updates in translational neurology.Frontiers in neurology · 2024Review
- Sturge-Weber syndrome: Updates in pathogenesis, diagnosis, and treatment.Annals of the Child Neurology Society · 2023Review
- Antibody blockade of Jagged1 attenuates choroidal neovascularization.Nature communications · 2023Article
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by vascular malformations affecting skin, eyes and leptomeninges of the brain, which can lead to glaucoma, seizures and intellectual disability. The discovery of a disease-causing somatic missense mutation in the GNAQ gene, encoding an alpha chain of heterotrimeric G-proteins, has initiated efforts to understand how G-proteins contribute to SWS pathogenesis. The mutation is predominantly detected in endothelial cells and is currently believed to affect downstream MAPK signalling. In this study of six Norwegian patients with classical SWS, we aimed to identify somatic mutations through deep sequencing of DNA from skin biopsies. Surprisingly, one patient was negative for the GNAQ mutation, but instead harbored a somatic mutation in GNB2 (NM_005273.3:c.232A>G, p.Lys78Glu), which encodes a beta chain of the same G-protein complex. The positions of the mutant amino acids in the G-protein are essential for complex reassembly. Therefore, failure of reassembly and continuous signalling is a likely consequence of both mutations. Ectopic expression of mutant proteins in endothelial cells revealed that expression of either mutant reduced cellular proliferation, yet regulated MAPK signalling differently, suggesting that dysregulated MAPK signalling cannot fully explain the SWS phenotype. Instead, both mutants reduced synthesis of Yes-associated protein (YAP), a transcriptional co-activator of the Hippo signalling pathway, suggesting a key role for this pathway in the vascular pathogenesis of SWS. The discovery of the GNB2 mutation sheds novel light on the pathogenesis of SWS and suggests that future research on targets of treatment should be directed towards the YAP, rather than the MAPK, signalling pathway.
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