Infevers: An evolving mutation database for auto-inflammatory syndromes

Touitou, Isabelle; Lesage, Suzanne; McDermott, Michael F.; Cuisset, Laurence; Hoffman, Hal M.; Dodé, Catherine; Shoham, Nitza G.; Aganna, Ebun; Hugot, Jean‐Pierre; Wise, Carol A.; Waterham, Hans R.; Pugnère, Denis; Demaille, Jacques; Menthière, Cyril Sarrauste de

doi:10.1002/humu.20080

Cited by 275 publications

(187 citation statements)

References 13 publications

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“…2 Genomic studies of MVK revealed missense mutations that have been already reported in patients with MKD, with the p.Val377Ile mutation as the most frequent. 3 Digestive manifestations are frequent during the course of HIDS. They are mostly transient; occur during a Values are given 1 mo after the onset of treatment.…”

Section: Discussionmentioning

confidence: 99%

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Levy

Arion²,

Berrebi

et al. 2013

Pediatrics

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Hyperimmunoglobulinemia D is the less severe form of mevalonate kinase deficiency (MKD) caused by recessive inherited mutation in the mevalonate kinase gene. Hyperimmunoglobulinemia D is characterized by febrile attacks, often associated with transient digestive manifestations, such as abdominal pain, diarrhea, and vomiting. Here we report for the first time 2 patients with MKD revealed by severe neonatal colitis. Both patients had chronic bloody diarrhea and failure to thrive; 1 patient since the age of 1 month and the other since the age of 12 days. Total parenteral nutrition was required. A marked elevation of acute phase reactants was present, and no evidence of infection was found. In patient 1, ileocolonoscopy revealed ulcerative colitis at the age of 5 months. Patient 2 suffered from enterocolitis and shock, associated with multiple bowel adhesions at age 5 weeks; the rectosigmoidoscopy showed aphtoid lesions of the sigmoid colon. Pathologic findings of colonic biopsies revealed a dense polymorph inflammatory infiltrate associated with deep ulcerations. Febrile attacks occurred 2 months after the onset of digestive symptoms in patient 1, and at onset of disease in patient 2. Genomic sequencing of the mevalonate kinase gene revealed compound heterozygous mutations in both patients. Anti-interleukin-1 agent produced longterm remission of all digestive features and laboratory parameters. This report emphasizes that MKD may be the cause of severe earlyonset inflammatory colitis, and must be considered by physicians, even in the absence of fever, after ruling out infections. Antiinterleukin-1 therapy may result in a dramatic improvement of MKD-related inflammatory bowel disease. Pediatrics 2013;132:e779-e783 AUTHORS:

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Section: Discussionmentioning

confidence: 99%

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Levy

Arion²,

Berrebi

et al. 2013

Pediatrics

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“…Thus far, many missense mutations in the CIAS1 gene have been identified in hereditary systemic autoinflammatory disorders. 28 However, an association between the CIAS1 gene and hypertension has not been reported. We used a case -control study using a singlecandidate-gene approach to determine whether the CIAS1 gene was associated with hypertension.…”

Section: Essential Hypertension (Eh [Min1455]mentioning

confidence: 99%

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension

et al. 2006

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Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-jB and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the first genetic study indicating an association between the CIAS1 gene and susceptibility to essential hypertension (EH). The frequency of subject with the homozygote of 12 repeat allele was significantly higher in patients with hypertension compared with control subjects (987 cases, 924 controls) (P ¼ 0.030; odds ratio ¼ 1.24) at a novel VNTR polymorphism of CIAS1 intron 4 loci. We also found that the mean of systolic blood pressure of homozygotes of 12 repeat allele was 6.4 mmHg higher than those of homozygotes of non-12 repeat allele in male random population (P ¼ 0.009). The frequency of six SNPs spanning of the CIAS1 gene was not significantly between patients and controls. The real-time PCR analysis showed that among healthy young adults, 12-12 subjects expressed CIAS1 mRNA in peripheral leukocytes significantly more abundantly than homozygote of non-12 repeat alleles subjects (Po0.05). Reporter gene assay of the CIAS1-VNTR in HL60 stimulated by lipopolysaccharides showed that the intronic sequence involving 12 repeat increased the expression of luciferase compared with 9, 7, and 6 repeats.

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“…Other autoinflammatory diseases include the cryopyrinopathies (or cryopyrin-associated periodic syndromes) linked to dominant active mutations in NLRP3/ cryopyrin, a component of the IL-1β-processing inflammasome. More common diseases, such as gout, systemic-onset juvenile idiopathic arthritis, and adult-onset Still's disease, also have been classified as autoinflammatory (5-7) More than 50 TNFRSF1A mutations associated with TRAPS have been described in the INFEVERS database (http://fmf.igh.cnrs.fr/ISSAID/infevers) (8). They are restricted to the extracellular domain of the receptor, with a striking absence of mutations that would result in loss of protein expression or truncation.…”

mentioning

confidence: 99%

Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome

Simon¹,

Park

Maddipati

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

174

151

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TNF, acting through p55 tumor necrosis factor receptor 1 (TNFR1), contributes to the pathogenesis of many inflammatory diseases. TNFR-associated periodic syndrome (TRAPS, OMIM 142680) is an autosomal dominant autoinflammatory disorder characterized by prolonged attacks of fevers, peritonitis, and soft tissue inflammation. TRAPS is caused by missense mutations in the extracellular domain of TNFR1 that affect receptor folding and trafficking. These mutations lead to loss of normal function rather than gain of function, and thus the pathogenesis of TRAPS is an enigma. Here we show that mutant TNFR1 accumulates intracellularly in peripheral blood mononuclear cells of TRAPS patients and in multiple cell types from two independent lines of knockin mice harboring TRAPSassociated TNFR1 mutations. Mutant TNFR1 did not function as a surface receptor for TNF but rather enhanced activation of MAPKs and secretion of proinflammatory cytokines upon stimulation with LPS. Enhanced inflammation depended on autocrine TNF secretion and WT TNFR1 in mouse and human myeloid cells but not in fibroblasts. Heterozygous TNFR1-mutant mice were hypersensitive to LPS-induced septic shock, whereas homozygous TNFR1-mutant mice resembled TNFR1-deficient mice and were resistant to septic shock. Thus WT and mutant TNFR1 act in concert from distinct cellular locations to potentiate inflammation in TRAPS. These findings establish a mechanism of pathogenesis in autosomal dominant diseases where full expression of the disease phenotype depends on functional cooperation between WT and mutant proteins and also may explain partial responses of TRAPS patients to TNF blockade. autoinflammatory disease | genetic disease

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Infevers: An evolving mutation database for auto-inflammatory syndromes

Cited by 275 publications

References 13 publications

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

Severe Early-Onset Colitis Revealing Mevalonate Kinase Deficiency

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension

Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome

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