ArticleAmerican journal of human genetics2019
Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Gene therapy for intracranial aneurysms: systemic review.Journal of neurointerventional surgery · 2025Pooled it
- Hemilateral adipose and muscular atrophy associated with a somatic PDGFRB p.N666K variant.Genes & diseases · 2026Article
- Tyrosine kinase inhibitors in Kosaki/Penttinen syndromes: new reports, follow-up of treated individuals and literature review.European journal of human genetics : EJHG · 2026Review
- Potential drug targets for intracranial aneurysms identified through Mendelian randomization analysis.Neurosurgical review · 2025Article
- Low-Allele-Frequency Somatic Variants in a Cohort of Sporadic Saccular "Berry" Cerebral Aneurysms.Journal of the American Heart Association · 2025Article
- Occurrence of fatal vertebrobasilar dolichoectasia after occlusion of unilateral internal carotid artery.BMC neurology · 2025Article
- Cancer-type somatic mutations in saccular cerebral aneurysms.European journal of human genetics : EJHG · 2025Article
- Infantile myofibromatosis and capillary malformation of the skin due to PDGFRB mosaicism.Molecular and cellular pediatrics · 2025Review
- Pan-cancer analysis of PDGFRB: Laying the foundation for the development of targeted immunotherapy drugs.Medicine · 2025Article
- Exploration of the shared gene signatures and molecular mechanisms between Alzheimer's disease and intracranial aneurysm.Scientific reports · 2024Article
- Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm.Journal of biomedical science · 2024Article
- Identification of differences in CD4Scientific reports · 2023Article
- Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.Frontiers in physiology · 2023Review
- Somatic Variants in SVIL in Cerebral Aneurysms.Neurology. Genetics · 2022Article
- Identifying and validating key genes mediating intracranial aneurysm rupture using weighted correlation network analysis and exploration of personalized treatment.Annals of translational medicine · 2022Article
- Endovascular Biopsy for Detection of Somatic Mosaicism in Human Fusiform Cerebral Aneurysms.Stroke (Hoboken, N.J.) · 2022Article
- Somatic Mosaicism of a PDGFRB Activating Variant in Aneurysms of the Intracranial, Coronary, Aortic, and Radial Artery Vascular Beds.Journal of the American Heart Association · 2022Article
- Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.Cardiovascular research · 2022Review
- Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies.Frontiers in immunology · 2022Review
- Somatic mosaicism in the MAPK pathway in sporadic brain arteriovenous malformation and association with phenotype.Journal of neurosurgery · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor β gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher's exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent auto-phosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors.
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