ArticleAmerican journal of human genetics2015
Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 2 of them syntheses that pooled it.
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Who cites it
133 citing papers in PubMed, 2 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.Nature communications · 2025Pooled it
- Oral Phenotype of Singleton-Merten Syndrome: A Systematic Review Illustrated With a Case Report.Frontiers in genetics · 2022Pooled it
- KLF5 Downregulation Links Impaired BNIP3-Mediated Mitophagy to Inflammatory Valve Remodeling in Calcific Aortic Valve Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- DDX3X induces mesenchymal transition of endothelial cells by disrupting BMPR2 signaling.FEBS open bio · 2026Article
- Aortoiliac and superior mesenteric artery narrowing and calcification in Singleton Merten syndrome.Radiology case reports · 2026Article
- SAVI: molecular mechanisms, clinical spectrum and precision medicine approaches beyond type-I IFN.Frontiers in immunology · 2026Review
- An autoinflammatory RIG-I variant causing Singleton-Merten syndrome associates with small non-coding Y-RNAs.Discovery immunology · 2026Article
- Mouse models of type I interferonopathies.Human molecular genetics · 2025Review
- Article
- ADAR1 haploinsufficiency and sustained picornaviral RdRp dsRNA synthesis synergize to dysregulate RNA editing and cause multi-system interferonopathy.bioRxiv : the preprint server for biology · 2025Article
- Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing.Nature cell biology · 2025Article
- Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus - focus on juvenile-onset systemic lupus erythematosus.Current opinion in rheumatology · 2025Review
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity.Immunological reviews · 2025Review
- Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024Review
- From Cells to Plaques: The Molecular Pathways of Coronary Artery Calcification and Disease.Journal of clinical medicine · 2024Review
- Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.Circulation · 2024Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.
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