Early-onset inflammatory bowel disease caused by loss-of-function mutations in the IL10-receptor genes

AbstractCARMIL2 is required for CD28-mediated co-stimulation of NF-κB signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelic CARMIL2 variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the same CARMIL2 null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missense CARMIL2 variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations. CARMIL2 should be included in the diagnostic work-up of patients with suspected monogenic IBD.

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Novel TNFAIP3 microdeletion in a girl with infantile-onset inflammatory bowel disease complicated by a severe perianal lesion

Human Genome Variation ◽

10.1038/s41439-020-00128-4 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Kosuke Taniguchi ◽

Mikihiro Inoue ◽

Katsuhiro Arai ◽

Keiichi Uchida ◽

Osuke Migita ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Bowel Disease ◽

Early Onset ◽

De Novo ◽

Loss Of Function ◽

Whole Exome ◽

Inflammatory Bowel

AbstractA20 haploinsufficiency (HA20), a disease caused by loss-of-function TNFAIP3 mutations, manifests various autoinflammatory and/or autoimmune symptoms. Some cases of HA20 were initially diagnosed as very early onset inflammatory bowel disease (VEO-IBD). We performed whole-exome sequencing (WES) for a Japanese girl with infantile-onset IBD and a severe perianal lesion and detected a novel de novo 119 kb microdeletion containing only TNFAIP3 (arr[GRCh37] 6q23.3(138125829_138244816) × 1).

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Faculty Opinions recommendation of Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718356707.793505968 ◽

2015 ◽

Author(s):

Ramsay Fuleihan ◽

Whitney Stevens

Keyword(s):

Inflammatory Bowel Disease ◽

Common Variable Immunodeficiency ◽

Bowel Disease ◽

Early Onset ◽

Inflammatory Bowel ◽

Common Variable

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Different renal manifestations associated with very early onset pediatric inflammatory bowel disease: case report and review of literature

BMC Nephrology ◽

10.1186/s12882-021-02358-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

A. Angeletti ◽

S. Arrigo ◽

A. Madeo ◽

M. Molteni ◽

E. Vietti ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Interstitial Nephritis ◽

Inflammatory Bowel Diseases ◽

Bowel Disease ◽

Early Onset ◽

Renal Involvement ◽

Granulomatous Interstitial Nephritis ◽

Disease Case ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Background Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract. In particular, Crohn disease and ulcerative colitis represent the two most common types of clinical manifestations. Extraintestinal manifestations of inflammatory bowel diseases represent a common complications, probably reflecting the systemic inflammation. Renal involvement is reported in 4–23% of cases. However, available data are limited to few case series and retrospective analysis, therefore the real impact of renal involvement is not well defined. Case presentation We report the case of a 10-years old male affected by very early onset unclassified-Inflammatory bowel diseases since he was 1-year old, presenting with a flare of inflammatory bowel diseases associated with acute kidney injury due to granulomatous interstitial nephritis. Of interest, at 7-year-old, he was treated for IgA nephropathy. To our knowledge, no previous reports have described a relapse of renal manifestation in inflammatory bowel diseases, characterized by two different clinical and histological phenotypes. Conclusions The link between the onset of kidney injuries with flares of intestinal inflammation suggest that nephritis maybe considered an extra-intestinal manifestation correlated with active inflammatory bowel disease. However, if granulomatous interstitial nephritis represents a cell-mediated hypersensitivity reaction than a true extraintestinal manifestation of inflammatory bowel diseases is still not clarified. We suggest as these renal manifestations here described may be interpreted as extraintestinal disorder and also considered as systemic signal of under treatment of the intestinal disease.

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A collaborative effort to define the epidemiology of pediatric inflammatory bowel disease: What can we learn from children with early-onset disease?

The Journal of Pediatrics ◽

10.1016/j.jpeds.2004.10.068 ◽

2005 ◽

Vol 146 (1) ◽

pp. 7-8 ◽

Cited By ~ 1

Author(s):

M. Susan Moyer

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Early Onset ◽

Collaborative Effort ◽

Pediatric Inflammatory Bowel Disease ◽

Inflammatory Bowel

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Expanding Contributions of Monogenic Very Early Onset Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab145 ◽

2021 ◽

Author(s):

Jodie Ouahed

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Early Onset ◽

Current Issue ◽

Epithelial Barrier ◽

Mevalonate Kinase Deficiency ◽

Bowel Diseases ◽

Life Threatening ◽

Mucosal Homeostasis ◽

Inflammatory Bowel

Abstract Currently over 70 genes known to be causative in very early onset inflammatory bowel disease (VEOIBD) have been identified. In the current issue of Inflammatory Bowel Diseases, 2 articles describing monogenetic forms of VEOIBD are highlighted. One describes a patient with life-threatening VEOIBD and a mutation in ITGA6, illustrating the importance of the epithelial barrier in maintaining mucosal homeostasis. The other describes the presentation and management of 10 patients with VEOIBD secondary to damaging mutations in MVK, resulting in mevalonate kinase deficiency. Though most monogenic causes of VEOIBD remain “private,” understanding the different categories of pathways affected in children with VEOIBD is critical and has already resulted in invaluable insight in the management of patients with VEOIBD and may hold strong implications for the care of IBD overall.

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Very early onset inflammatory bowel disease (VEO-IBD); spectrum of clinical presentation, diagnostic tools and outcome in children

Journal of the Pakistan Medical Association ◽

10.47391/jpma.05-725 ◽

2021 ◽

Vol 71 (10) ◽

pp. 2350-2354

Author(s):

Huma Arshad Cheema ◽

Nadia Waheed ◽

Anjum Saeed ◽

Zafar Fayyaz ◽

Muhammad Nadeem Anjum ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Early Onset ◽

Clinical Presentation ◽

Association Studies ◽

Diagnostic Tools ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Basic Work ◽

Inflammatory Bowel

Background: Very early-onset inflammatory bowel disease (VEO-IBD) is defined as diagnosis of Ulcerative Colitis (UC) or Crohn’s Disease (CD) in children under six years of age. Genome wide association studies have linked a strong genetic component responsible for VEO-IBD. Approximately, 30-40% children of VEO-IBD have underlying immunodeficiency states. We aimed to study the spectrum of presentation, underlying monogenetic defects and outcome in VEO-IBD. Methods: This is a prospective, observational study conducted at division of Gastroenterology, the Children's Hospital & the Institute of Child Health, Lahore, over 2 years. Children developing features of IBD under six-years of age were included. Data included demography, clinical presentation, diagnostic tools and outcome. Gastroscopy and colonoscopy were performed in all patients in addition to basic work up done for associatedimmunodeficiency states and molecular genetics. SPSS version 21 was used for analysis. Continuous...

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