ArticleAmerican journal of human genetics2013
Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322165 (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions), which is not on this map. Cited by 143 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
Who cites it
143 citing papers in PubMed, 4 syntheses or guidelines pooled it, 243 citations in OpenAlex.
- 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.The Journal of thoracic and cardiovascular surgery · 2023Guideline
- 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2022Guideline
- Guideline
- Systematic Review of Studies That Have Evaluated Screening Tests in Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Disease.Journal of the American Heart Association · 2018Pooled it
- Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.Scientific reports · 2019Trial
- Gene-Based Rare Variant Burden Analyses Across Biobanks Identify Novel High-Risk Genes for Thoracic Aortic Disease.medRxiv : the preprint server for health sciences · 2026Article
- Aortic disease-linked mutations reveal unexpected convergent allosteric mechanisms of protein kinase G misregulation.Science advances · 2026Article
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Genetic and molecular mechanisms of hereditary thoracic aortic aneurysm and dissection (Review).Molecular medicine reports · 2026Review
- Dynamic stiffness enables stage-specific properties mediating functional endothelialization on vascular implants.Science advances · 2026Article
- Heritable Thoracic Aortic Diseases in Pediatric Practice: From Molecular Mechanisms to Genotype-Informed Management, a Comprehensive Narrative Review.Journal of clinical medicine · 2026Review
- Growth arrest of thoracic aortic aneurysms in aging Marfan mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses.Genes · 2026Review
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Use of soluble guanylyl cyclase stimulators in heart failure therapy-a mode of action perspective.ESC heart failure · 2026Review
- MYH11 variants in thoracic aortic aneurysm pathophysiology: From bench to bedside.European journal of clinical investigation · 2026Review
- Article
- A Pathogenic ROCK-Signaling Network Involving a Lysine Deletion in Myh11 Renders Carriers Susceptible to Aortic Dissection.International journal of molecular sciences · 2026Article
- Characterization of a New PRKG1 Mutation Associated With Thoracic Aortic Aneurysm and Dissection.JACC. Basic to translational science · 2026Article
- CNP-induced cGMP signaling reduces growth cone stiffness and CaFrontiers in molecular neuroscience · 2026Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 8 institutions in 3 countries.
Funding
Abstract
Gene mutations that lead to decreased contraction of vascular smooth-muscle cells (SMCs) can cause inherited thoracic aortic aneurysms and dissections. Exome sequencing of distant relatives affected by thoracic aortic disease and subsequent Sanger sequencing of additional probands with familial thoracic aortic disease identified the same rare variant, PRKG1 c.530G>A (p.Arg177Gln), in four families. This mutation segregated with aortic disease in these families with a combined two-point LOD score of 7.88. The majority of affected individuals presented with acute aortic dissections (63%) at relatively young ages (mean 31 years, range 17-51 years). PRKG1 encodes type I cGMP-dependent protein kinase (PKG-1), which is activated upon binding of cGMP and controls SMC relaxation. Although the p.Arg177Gln alteration disrupts binding to the high-affinity cGMP binding site within the regulatory domain, the altered PKG-1 is constitutively active even in the absence of cGMP. The increased PKG-1 activity leads to decreased phosphorylation of the myosin regulatory light chain in fibroblasts and is predicted to cause decreased contraction of vascular SMCs. Thus, identification of a gain-of-function mutation in PRKG1 as a cause of thoracic aortic disease provides further evidence that proper SMC contractile function is critical for maintaining the integrity of the thoracic aorta throughout a lifetime.
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What OpenQuestion holds
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.