ArticleArthritis & rheumatology (Hoboken, N.J.)2017
Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Oral Phenotype of Singleton-Merten Syndrome: A Systematic Review Illustrated With a Case Report.Frontiers in genetics · 2022Pooled it
- Establishing the molecular basis for MDA5 mutation-linked autoimmunity.Nucleic acids research · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- 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
- Jaccoud arthropathy with anti-TIF1-γ-positive clinically amyopathic dermatomyositis: A rare association.JAAD case reports · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study.Pediatric rheumatology online journal · 2024Article
- JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases.Journal of clinical medicine · 2023Review
- A zebrafish model of Ifih1-driven Aicardi-Goutières syndrome reproduces the interferon signature and the exacerbated inflammation of patients.Frontiers in immunology · 2023Article
- Anti-MDA5 dermatomyositis: an update from bench to bedside.Current opinion in rheumatology · 2022Review
- Article
- STING-Mediated Lung Inflammation and Beyond.Journal of clinical immunology · 2021Review
- Immunogenetics of the Ocular Anterior Segment: Lessons from Inherited Disorders.Journal of ophthalmology · 2021Review
- Case Report: Aicardi-Goutières Syndrome and Singleton-Merten Syndrome Caused by a Gain-of-Function Mutation in IFIH1.Frontiers in genetics · 2021Article
- Lung involvement in monogenic interferonopathies.European respiratory review : an official journal of the European Respiratory Society · 2020Article
- Monogenic autoinflammatory disorders: Conceptual overview, phenotype, and clinical approach.The Journal of allergy and clinical immunology · 2020Review
- [Classification of autoinflammatory diseases based on pathophysiological mechanisms].Zeitschrift fur Rheumatologie · 2020Review
- Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung disease: report of a new phenotype.Pediatric rheumatology online journal · 2020Article
- Genetic and phenotypic spectrum associated with IFIH1 gain-of-function.Human mutation · 2020Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
objectiveTo define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet, including camptodactyly, subluxation, and tendon rupture, reminiscent of Jaccoud's arthropathy.
methodsWe identified 2 families segregating an autosomal-dominant phenotype encompassing musculoskeletal disease and variable additional features, including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma, and basal ganglia calcification. We measured the expression of interferon (IFN)-stimulated genes in the peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA-5). We also assessed the functional consequences of IFIH1 gene variants using an in vitro IFNβ reporter assay in HEK 293T cells.
resultsWe recorded an up-regulation of type I IFN-induced gene transcripts in all 5 patients tested and identified a heterozygous gain-of-function mutation in IFIH1 in each family, resulting in different substitutions of the threonine residue at position 331 of MDA-5. Both of these variants were associated with increased IFNβ expression in the absence of exogenous dsRNA ligand, consistent with constitutive activation of MDA-5.
conclusionThese cases highlight the significant musculoskeletal involvement that can be associated with mutations in MDA-5, and emphasize the value of testing for up-regulation of IFN signaling as a marker of the underlying molecular lesion. Our data indicate that both Singleton-Merten syndrome and neuroinflammation described in the context of MDA-5 gain-of-function constitute part of the same type I interferonopathy disease spectrum, and provide possible novel insight into the pathology of Jaccoud's arthropathy.
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