IFIH1 and DDX58 gene variants in pediatric rheumatic diseases  

作　　者：Rinat Raupov Evgeny Suspitsin Konstantin Belozerov Tatiana Gabrusskaya Mikhail Kostik 

机构地区：[1]Department of Pediatry,Saint-Petersburg State Pediatric Medical University,Saint-Petersburg 194100,Russia [2]Department of Genetics,Saint-Petersburg State Pediatric Medical University,Saint-Petersburg 194100,Russia [3]Department of Gastrointestinal Diseases,Saint-Petersburg State Pediatric Medical University,Saint-Petersburg 194100,Russia

出　　处：《World Journal of Clinical Pediatrics》2023年第3期107-114,共8页世界临床儿科杂志

摘　　要：BACKGROUND The IFIH1 gene codes the MDA5 protein and the DDX58 gene codes the RIG-I receptor.Both proteins are parts of the interferon(IFN)I signaling pathway and are responsible for antiviral defense and innate immune response.IFIH1 and DDX58 polymorphisms are associated with a spectrum of autoimmune diseases.Rare gain-of-function IFIH1 mutations have been found in Singleton-Merten and Aicardi-Goutières syndrome,while DDX58 mutation can cause atypical Singleton-Merten syndrome.AIM To characterize children with pediatric rheumatic diseases(PRD)carrying DDX58 or IFIH1 variants.METHODS Clinical exome sequencing was performed on 92 children with different PRD.IFIH1 and DDX58 variants have been detected in 14 children.IFN-I score has been analyzed and the clinical characteristics of patients have been studied.RESULTS A total of seven patients with systemic lupus erythematosus(SLE)(n=2),myelodysplastic syndrome with SLE features at the onset of the disease(n=1),mixed connective tissue disease(MCTD)(n=1),undifferentiated systemic autoinflammatory disease(uSAID)(n=3)have 5 different variants of the DDX58 gene.A common non-pathogenic variant p.D580E has been found in five children.A rare variant of uncertain significance(VUS)p.N354S was found in one patient with uSAID,a rare likely non-pathogenic variant p.E37K in one patient with uSAID,and a rare likely pathogenic variant p.Cys864fs in a patient with SLE.Elevated IFN-I score was detected in 6 of 7 patients with DDX58 variants.Seven patients had six different IFIH1 variants.They were presented with uSAID(n=2),juvenile dermatomyositis(JDM)(n=1),SLElike disease(n=1),Periodic fever with aphthous stomatitis,pharyngitis,and adenitis syndrome(n=1),and systemic onset juvenile idiopathic arthritis(n=1).Three patients have VUS p.E627X,one patient has benign variant p.I923V.Rare VUS p.R595H was detected in the JDM patient.Another rare VUS p.L679Ifs*2 and previously not reported variant p.V599Ffs*5 were detected in the patient with uSAID.One patient with uSAID has rare VUS p.T520A

关 键 词：IFIH1 DDX58 Undifferentiated systemic autoinflammatory disease Systemic lupus erythematosus Interferon-I score©The Author(s)2023.Published by Baishideng 

分 类 号：R725.9[医药卫生—儿科]