scholarly journals Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luca Bosa ◽  
Vritika Batura ◽  
Davide Colavito ◽  
Karoline Fiedler ◽  
Paola Gaio ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Clinical Signs ◽  
Missense Variant ◽  
Loss Of Function ◽  
Altered Expression ◽  
Autoimmune Polyendocrine Syndrome ◽  
Altered Expression Pattern ◽  
Inflammatory Bowel

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.

IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease

2021 ◽  
Author(s):  
Mara Cananzi ◽  
Elizabeth Wohler ◽  
Antonio Marzollo ◽  
Davide Colavito ◽  
Jing You ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Loss Of Function ◽  
Inflammatory Bowel

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

2009 ◽  
Vol 15 ◽  
pp. S56 ◽  
Author(s):  
E Glocker ◽  
D Kotlarz ◽  
K Boztug ◽  
E Gertz ◽  
A Schaffer ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Loss Of Function ◽  
Inflammatory Bowel

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

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).

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

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.

scholarly journals Altered expression of cell adhesion molecules in uninvolved gut in inflammatory bowel disease

2008 ◽  
Vol 94 (2) ◽  
pp. 341-347 ◽  
Author(s):  
G. M. SCHUERMANN ◽  
A. E. ABER-BISHOP ◽  
P. FACER ◽  
J. C. LEE ◽  
D. S. RAMPTON ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Bowel Disease ◽  
Cell Adhesion Molecules ◽  
Altered Expression ◽  
Inflammatory Bowel

Altered expression of fucosyl-transferases in inflammatory bowel disease

2001 ◽  
Vol 120 (5) ◽  
pp. A525
Author(s):  
Keith Leiper ◽  
Sameena Javeed ◽  
Yamini Krishna ◽  
Jonathan M. Rhodes ◽  
Barry J. Campbell
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Altered Expression ◽  
Inflammatory Bowel

Expanding Contributions of Monogenic Very Early Onset Inflammatory Bowel Disease

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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