scholarly journals The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Neel Dhingani ◽  
Conghui Guo ◽  
Jie Pan ◽  
Qi Li ◽  
Neil Warner ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Intestinal Atresia ◽  
Compound Heterozygous ◽  
Functional Studies ◽  
Monogenic Disorders ◽  
Whole Exome ◽  
Inflammatory Bowel ◽  
Tetratricopeptide Repeat Domain

Abstract Very early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.

Compound Heterozygous IL10RA Mutations in Brothers with Very Early Onset Inflammatory Bowel Disease

2012 ◽  
Vol 18 ◽  
pp. S81
Author(s):  
Julia Bracken ◽  
Darrel Dinwiddie ◽  
Kathy Christenson ◽  
Charles Roberts ◽  
Carol Saunders ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Compound Heterozygous ◽  
Inflammatory Bowel

scholarly journals Sequence Analysis of TNFRSF13b, Encoding TACI, in a Patient with Very Early Onset Inflammatory Bowel Disease: a Case Report

2018 ◽  
Vol 1 (4) ◽  
pp. 110
Author(s):  
Jiaying Shen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Clinical Laboratory ◽  
Histopathological Examination ◽  
Immunosuppressive Treatment ◽  
Poor Response ◽  
Compound Heterozygous ◽  
Inflammatory Bowel ◽  
Compound Heterozygous Mutations

Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed before 6 years of age, frequently presents with increased severity, aggressive progression, and often poor response to conventional treatments. Although the cause of IBD is generally considered to be intestinal immune dysfunction induced by polygenic mutations and environment and other factors, VEO-IBD has a stronger genetic susceptibility specifically the neonatal- or infantile-onset IBD. Herein we report compound heterozygous mutations in the tumor necrosis factor receptor superfamily member 13b (TNFRSF13B) gene in a 3-year-old male that was admitted to our hospital with lasted jaundice, repeated fever and diarrhea in May 2014 at 2-month-old. He was diagnosed with VEO-IBD based on clinical, laboratory and histopathological examination. However, he was unresponsive to the conventional therapy, including the nutritional support therapy, antibiotic and immunosuppressive treatment, and surgical release of neonatal intestinal obstruction. Novel compound heterozygous mutations, c.[365G>A];[452C>T](p.[R122Q];[P151L]), were discovered in TNFRSF13B, encoding TACI, for this patient.

scholarly journals Phenotype of Very-Early-Onset Inflammatory Bowel Disease with Interleukin-10 Receptor A Mutations in 22 Chinese Children

2020 ◽  
Author(s):  
Dexiu Guan ◽  
Jing Zhang ◽  
Shu Guo ◽  
Feihong Yu ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Cord Blood Transplantation ◽  
Gene Mutations ◽  
Onset Time ◽  
Interleukin 10 ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Inflammatory Bowel

Abstract Backgroud: Very-early-onset inflammatory bowel disease (VEO-IBD) with onset in infancy may be caused by genetic mutation. We collected the VEO-IBD patients with interleukin-10 receptor A (IL-10RA) gene mutations to investigate the clinical phenotype and genetic characteristics.Methods: The data of 22 patients with VEO-IBD with IL-10RA gene mutations were retrospectively analyzed, and high-throughput sequencing was used to identify IL-10RA gene mutations.Results: All 22 patients in this study had IL-10RA gene mutations, including 4 (18.2%) homozygous mutations and 18 (81.8%) compound heterozygous mutations. Among these mutations, 10 mutations had been previously described and 1 novel mutation was identified. In these patients, c.C301T (p.R101W) (86.4%, 19/22) and c.G537A (p.T179T) (36.4%, 8/22) mutations were the most common mutations. This study showed that the patients had extremely early onset of symptoms, about 81.8% (18/22) of the patients had onset within 1 month after birth, and the onset time was 8.5 (IQR: 3.0–24.0) days. In addition, 77.3% (17/22) of patients had recurrent perianal lesions. Oral ulcers and skin rash were common extra-intestinal manifestations, accounting for 72.7% (16/22) and 63.6% (14/22), respectively. In this study, 3 patients underwent enterostomy and 1 patient experienced intestinal perforation repair. Umbilical cord blood transplantation (UCBT) and thalidomide proved efficacious. Follow-up showed the mortality rate was as high as 45% (9/20).Conclusions: We should consider the genetic defects in the IL-10 signaling pathway in VEO-IBD patients, particularly when they had early onset of symptoms, perianal lesions and severe colitis.

scholarly journals Case Report: A Novel Compound Heterozygous Mutation in IL-10RA in a Chinese Child With Very Early-Onset Inflammatory Bowel Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Fang Dong ◽  
Fangfei Xiao ◽  
Ting Ge ◽  
Xiaolu Li ◽  
Wuhen Xu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Peripheral Blood ◽  
Early Onset ◽  
Compound Heterozygote ◽  
Chinese Child ◽  
Compound Heterozygous ◽  
Primary Immune Deficiency ◽  
Hematopoietic Stem ◽  
Inflammatory Bowel

Very early-onset inflammatory bowel disease (VEO-IBD) is defined as IBD diagnosed in children younger than 6 years of age. VEO-IBD is often associated with a monogenic etiology or primary immune deficiency. Here, we report the case of a 7-month-old Chinese girl diagnosed with VEO-IBD who had a variant in the interleukin-10 receptor A (IL-10-RA) gene. The patient presented with recurrent fevers, abdominal pain, diarrhea, perianal abscesses, and oral ulcers. Whole-exome sequencing (WES) identified a novel compound heterozygote mutation, c.395T>G (p.Leu132Arg)/ex.1del (p.?), in the IL-10RA gene of the patient. The missense mutation c.395T>G (p.Leu132Arg) was inherited from her mother, and ex.1del (p.?) was inherited from her father. Neither mutation has been reported previously. The IL-10RA function of the patient was defective, as demonstrated by a failure of signal transducer and activator of transcription 3 (STAT3) activation in peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IL-10. The patient underwent matched unrelated peripheral blood hematopoietic stem cell transplantation (HSCT), and the clinical manifestations were dramatically improved. In summary, we identified a novel compound heterozygote mutation, c.395T>G (p.Leu132Arg)/ex.1del (p.?), in IL-10RA that caused VEO-IBD in a Chinese child, which further expands the mutational spectrum of IL-10RA.

718 Whole Exome Sequencing in Cohort of Very Early Onset Inflammatory Bowel Disease

2014 ◽  
Vol 146 (5) ◽  
pp. S-125
Author(s):  
Christopher J. Moran ◽  
Judith R. Kelsen ◽  
Jess L. Kaplan ◽  
Mariah Baril-Dore ◽  
Elizabeth Petit ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Bowel Disease ◽  
Early Onset ◽  
Whole Exome ◽  
Inflammatory Bowel

scholarly journals Mutations in Tetratricopeptide Repeat Domain 7A Result in a Severe Form of Very Early Onset Inflammatory Bowel Disease

2014 ◽  
Vol 146 (4) ◽  
pp. 1028-1039 ◽  
Author(s):  
Yaron Avitzur ◽  
Conghui Guo ◽  
Lucas A. Mastropaolo ◽  
Ehsan Bahrami ◽  
Hannah Chen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Severe Form ◽  
Tetratricopeptide Repeat ◽  
Repeat Domain ◽  
Inflammatory Bowel ◽  
Tetratricopeptide Repeat Domain

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.

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