ArticleAnnals of the rheumatic diseases2022
Gain-of-function mutations in
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 38 papers.
0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
9.7field-weighted citation impact, top 1% of its field
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Whole exome sequencing of paediatric patients with Cogan's syndrome to identify monogenic mimics.Rheumatology (Oxford, England) · 2026Article
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- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Renal Disease in ROSAH Syndrome Masquerading as Lupus Nephritis: A Case Report and Cohort Analysis.Kidney medicine · 2026Article
- Irreversible Ocular and Systemic Damage in ROSAH Syndrome.Ophthalmology and therapy · 2026Article
- Article
- A novel de novo RNF13 variant in developmental and epileptic encephalopathy 73: genotype-phenotype correlation and literature review.BMC neurology · 2026Review
- Bcl-2 inhibitor resistance in diffuse large b-cell lymphoma: establishing a prognostic signature and targeting alpha protein kinase 1.Frontiers in oncology · 2026Article
- Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.ImmunoTargets and therapy · 2026Review
- Loss of alpha-kinase 1 contributes to the formation of congenital cataracts in mice.Cellular & molecular biology letters · 2025Article
- Tocilizumab as a treatment tool for ROSAH syndrome: a case report.Journal of ophthalmic inflammation and infection · 2025Article
- Stereoselective Anomeric Phosphorylation under Modified Mitsunobu Reaction Conditions.The Journal of organic chemistry · 2025Article
- Investigating the role of the ALPK1 signaling pathway in the pathogenesis of diabetic retinopathy.Scientific reports · 2025Article
- Discovery of a selective alpha-kinase 1 inhibitor for the rare genetic disease ROSAH syndrome.Nature communications · 2025Article
- The importance of ALPK1 kinase functionality as a potential biomarker for inflammatory diseases.Molecular biology reports · 2025Review
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- Article
- Sensing danger in the islet: the roles of pattern recognition receptors in β cells and type 1 diabetes.Frontiers in immunology · 2025Review
- Explore on the Mechanism of miRNA-146a/TAB1 in the Regulation of Cellular Apoptosis and Inflammation in Ulcerative Colitis Based on NF-κB Pathway.Current molecular medicine · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
71 authors at 20 institutions in 8 countries.
Christina Torres KozyckiInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA christina.kozycki@nih.gov dan.kastner@nih.gov.ORCID http://orcid.org/0000-0001-5405-4694
Shilpa KodatiNational Eye Institute, Bethesda, Maryland, USA.
Laryssa HurynNational Eye Institute, Bethesda, Maryland, USA.
Hongying WangInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Blake M WarnerNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-4961-018X
Priyam JaniNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Dima HammoudRadiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Mones S Abu-AsabSection of Histopathology, National Eye Institute, Bethesda, Maryland, USA.
Yingyos JittayasothornNational Eye Institute, Bethesda, Maryland, USA.
Mary J MattapallilNational Eye Institute, Bethesda, Maryland, USA.
Wanxia Li TsaiNational Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.
Ehsan UllahOphthalmic Genetics & Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA.
Ping ZhouNational Institute of Biological Sciences Beijing, Beijing, China.
Xiaoying TianNational Institute of Biological Sciences Beijing, Beijing, China.
Ariane SoldatosNational Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Niki MoutsopoulosNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Marie Kao-HsiehNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Theo HellerNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.
Edward W CowenDermatology Branch, NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.
Chyi-Chia Richard LeeNational Cancer Institute, Bethesda, Maryland, USA.
Camilo ToroUndiagnosed Diseases Program, Bethesda, Maryland, USA.
Shelley KalsiNational Heart Lung and Blood Institute, Bethesda, Maryland, USA.
Zohreh KhavandgarNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Alan BaerNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Margaret BeachNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Debra Long PrielNeutrophil Monitoring Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Michele NehrebeckyInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Sofia RosenzweigInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Tina RomeoInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Natalie DeuitchInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Laurie BrenchleyNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Eileen PelayoNational Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA.
Wadih ZeinNational Eye Institute, Bethesda, Maryland, USA.
Nida SenNational Eye Institute, Bethesda, Maryland, USA.
Alexander H YangNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.
Gary FarleyDrs. Gilbert and Farley, OD, PC, Colonial Heights, Virginia, USA.
David A SweetserMassachusetts General Hospital Center for Genomic Medicine, Boston, Massachusetts, USA.
Lauren BriereMassachusetts General Hospital Center for Genomic Medicine, Boston, Massachusetts, USA.
Janine YangMassachusetts Eye and Ear, Boston, Massachusetts, USA.
Fabiano de Oliveira PoswarHospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Ida Vanessa D SchwartzHospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Tamires Silva AlvesHospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Perrine DusserService de Rhumatologie Pédiatrique, Centre de Référence des Maladies Auto-Inflammatoires de l'enfant, Hôpital Bicêtre, AP HP, Université Paris Sud, Bicetre, France.
Isabelle Koné-PautService de Rhumatologie Pédiatrique, Centre de Référence des Maladies Auto-Inflammatoires et de l'amylose inflammatoire CEREMAIA, Hôpital Bicêtre, AP HP, Université Paris Saclay, Bicetre, France.ORCID http://orcid.org/0000-0001-8939-5763
Isabelle TouitouCeRéMAIA, CHU Montpellier, INSERM, University of Montpellier, Montpellier, France.
Salah Mohamed TitahHôpital Fondation Adolphe de Rothschild, Paris, France.
Petrus Martin van HagenDepts Internal Medicine and Immunology, Erasmus MC, Rotterdam, The Netherlands.
Rogier T A van WijckPathology & Clinical Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
Peter J van der SpekPathology & Clinical Bioinformatics, Erasmus MC, Rotterdam, The Netherlands.
Hiromi YanoIizuka Hospital, Iizuka, Japan.
Andreas BennecheDepartment of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Ellen M ApalsetBergen Group of Epidemiology and Biomarkers in Rheumatic Disease, Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
Ragnhild Wivestad JanssonDepartment of Ophthalmology, Haukeland University Hospital, Bergen, Norway.
Rachel R CaspiLaboratory of Immunology, National Eye Institute, NIH, Bethesda, Maryland, USA.
Douglas Byron KuhnsNeutrophil Monitoring Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Massimo GadinaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.
Hidetoshi TakadaDepartment of Child Health, University of Tsukuba Faculty of Medicine, Tsukuba, Japan.
Hiroaki IdaDivision of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Ryuta NishikomoriDepartment of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
Elena VerrecchiaDepartment of Internal Medicine, Periodic Fevers Research Center, Università Cattolica del Sacro Cuore, Roma, Italy.
Eugenio SangiorgiIstitute of Genomic di Medicine, Universita Cattolica del Sacro Cuore, Roma, Italy.
Raffaele MannaDepartment of Internal Medicine, Periodic Fevers Research Center, Università Cattolica del Sacro Cuore, Roma, Italy.
Brian P BrooksOphthalmic Genetics & Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA.
Lucia SobrinMassachusetts Eye and Ear, Boston, Massachusetts, USA.
Robert B HufnagelOphthalmic Genetics & Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA.
David BeckNYU, New York, New York, USA.
Feng ShaoNational Institute of Biological Sciences Beijing, Beijing, China.
Amanda K OmbrelloInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Ivona AksentijevichInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Daniel L KastnerInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA christina.kozycki@nih.gov dan.kastner@nih.gov.ORCID http://orcid.org/0000-0001-7188-4550
Undiagnosed Diseases Network
National Eye Institute · USNational Human Genome Research Institute · USNational Institute of Dental and Craniofacial Research · USErasmus MC · NLHaukeland University Hospital · NOMassachusetts Eye and Ear Infirmary · USMassachusetts General Hospital · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USNational Institute of Biological Sciences, Beijing · CNUniversità Cattolica del Sacro Cuore · ITFrederick National Laboratory for Cancer Research · USKurume University · JPNational Institute of Diabetes and Digestive and Kidney Diseases · USUniversidade Federal do Rio Grande do Sul · BRAso Iizuka Hospital · JPHospital de Clínicas de Porto Alegre · BRInserm · FRNational Cancer Institute · USNational Heart Lung and Blood Institute · USNational Institute of Neurological Disorders and Stroke · US
Funding
Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6MGenetic, Cellular and Molecular Mechanisms in Autoimmunity to RetinaZIAEY000184 · NEI · NATIONAL EYE INSTITUTE · PI CASPI, RACHEL R. · 2009 to 2025
$51.7MTranslational Immunology research: a support for clinical immunological researchZICAR041181 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI GADINA, MASSIMO · 2009 to 2025
$31.5MClinical Investigations of Sjogren's SyndromeZIADE000704 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI WARNER, BLAKE · 2009 to 2025
$22.3MGenetics, Pathophysiology, and Treatment of Dominant Autoinflammatory DiseasesZIAHG200373 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2024
$21.0MFlow cytometry support to research in immune, skin, muscle and bone diseasesZICAR041169 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI DELL'ORSO, STEFANIA · 2009 to 2025
$20.4MMechanisms of Chronic Inflammation in PeriodontitisZIADE000736 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI MOUTSOPOULOS, NIKI · 2010 to 2025
$14.1MOral Microbial and Immunological Characterization of Patients with Immune DysfunZIADE000732 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI MOUTSOPOULOS, NIKI · 2010 to 2024
$13.2MStudies of Ocular inflammation: Translational ResearchZIAEY000556 · NEI · NATIONAL EYE INSTITUTE · PI CASPI, RACHEL R. · 2017 to 2025
$11.3MCenter for Integrated Approaches to Undiagnosed DiseasesU01HG007690 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2014 to 2022
$10.4MUCLA clinical site for the investigation of undiagnosed disordersU01HG007703 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2014 to 2022
$10.1MClinical ophthalmic molecular diagnostics and discoveryZIAEY000564 · NEI · NATIONAL EYE INSTITUTE · PI GUAN, BIN · 2019 to 2025
$7.9MIntramural NIH HHS Z01 DE000704NHGRI NIH HHS U01 HG007690NHGRI NIH HHS U01 HG007703
Abstract
objectivesTo test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in
methodsThis cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of
resultsThe majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the
conclusionROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in
Indexed as
Hereditary Autoinflammatory DiseasesNF-kappa BAmyloidosisAnimalsCohort StudiesGain of Function MutationHumansInflammationMiceMutationProtein KinasesQuality of LifeSerum Amyloid A ProteinSyndromeTumor Necrosis Factor InhibitorsALPK1 protein, mouseNF-kappa BProtein KinasesSerum Amyloid A ProteinTumor Necrosis Factor InhibitorsAmyloidosisArthritisImmune System DiseasesInflammationTherapeutics
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Read underepoch 390
Registered trials
NCT02450851ClinicalTrials.gov
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.