ArticleAmerican journal of human genetics2015
A specific IFIH1 gain-of-function mutation causes 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 129 papers, 3 of them syntheses that pooled it.
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Who cites it
129 citing papers in PubMed, 3 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.Nature communications · 2025Pooled it
- Shared genetic risk factors and causal association between psoriasis and coronary artery disease.Nature communications · 2022Pooled it
- Oral Phenotype of Singleton-Merten Syndrome: A Systematic Review Illustrated With a Case Report.Frontiers in genetics · 2022Pooled it
- IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease.Human genetics · 2021Trial
- Establishing the molecular basis for MDA5 mutation-linked autoimmunity.Nucleic acids research · 2026Article
- Molybdenum Nanoparticles Alleviate Psoriasis-Related Cardiovascular Oxidative Stress and Inflammation.ACS omega · 2026Article
- Adenosine-to-Inosine (A-to-I) RNA Editing by ADAR1 to Control RNA Sensing in Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- MDA5 generates compact ribonucleoprotein complexes via ATP-dependent double-stranded RNA unwinding.Nucleic acids research · 2026Article
- Aortoiliac and superior mesenteric artery narrowing and calcification in Singleton Merten syndrome.Radiology case reports · 2026Article
- MDA5 regulates BCR signaling and B-cell function via NF-κB-mediated DNM1.Cellular & molecular immunology · 2026Article
- Utilising Next-Generation Sequencing to Explore the Molecular Etiology of Short Root Anomaly.Orthodontics & craniofacial research · 2025Article
- Mouse models of type I interferonopathies.Human molecular genetics · 2025Review
- Article
- Psoriasis.Nature reviews. Disease primers · 2025Review
- Molecular basis of autoimmune disease protection by MDA5 variants.Cell reports · 2025Article
- MDA5 variants trade antiviral activity for protection from autoimmune disease.BMC medical genomics · 2025Article
- 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
- Cardiodermatology: the heart of the connection between the skin and cardiovascular disease.Nature reviews. Cardiology · 2025Review
- Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense.International journal of molecular sciences · 2025Review
- Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Singleton-Merten syndrome (SMS) is an infrequently described autosomal-dominant disorder characterized by early and extreme aortic and valvular calcification, dental anomalies (early-onset periodontitis and root resorption), osteopenia, and acro-osteolysis. To determine the molecular etiology of this disease, we performed whole-exome sequencing and targeted Sanger sequencing. We identified a common missense mutation, c.2465G>A (p.Arg822Gln), in interferon induced with helicase C domain 1 (IFIH1, encoding melanoma differentiation-associated protein 5 [MDA5]) in four SMS subjects from two families and a simplex case. IFIH1 has been linked to a number of autoimmune disorders, including Aicardi-Goutières syndrome. Immunohistochemistry demonstrated the localization of MDA5 in all affected target tissues. In vitro functional analysis revealed that the IFIH1 c.2465G>A mutation enhanced MDA5 function in interferon beta induction. Interferon signature genes were upregulated in SMS individuals' blood and dental cells. Our data identify a gain-of-function IFIH1 mutation as causing SMS and leading to early arterial calcification and dental inflammation and resorption.
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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.