Autosomal recessive 333 base pair interleukin 10 receptor alpha subunit deletion in very early-onset inflammatory bowel disease

Abstract Background : Infantile-onset inflammatory bowel disease (IO-IBD) patients with interleukin-10/interleukin-10 receptor (IL-10/IL-10R) mutations suffer from more severe and intractable disease. We aimed to investigate the clinical phenotypes and genotypic characteristics of IO-IBD patients with IL-10RA gene mutations. Methods : Data on 22 patients with IO-IBD with IL-10RA gene mutations were retrospectively analyzed, and high-throughput sequencing was used to identify the IL-10RA gene mutations. Results : In 22 patients with IO-IBD with IL-10RA mutations, c.C301T (p.R101W) (86.4%, 19/22) and c.G537A (p.T179T) (36.4%, 8/22) were the most common ones, and one novel mutation was identified (c.635G>C (p.R212P)). Patients had extremely early onset of symptoms, with 81.8% (18/22) having disease onset within 1 month after birth, and median onset time was 8.5 (interquartile range: 3.0–24.0) days. In addition, 77.3% (17/22) of patients had recurrent perianal lesions. Oral ulcers and skin rashes were common extra-intestinal manifestations, accounting for 72.7% (16/22) and 63.6% (14/22), respectively. In this study, three patients underwent enterostomy and one experienced intestinal perforation repair. Thalidomide was used in five patients in this study: one achieved clinical remission, three were clinical improvement and one still had disease activity. Two patients underwent umbilical cord blood transplantation (UCBT) and remained stable. Follow-up showed that the mortality rate was as high as 45% (9/20). Conclusions : In 22 IO-IBD patients with IL-10RA mutations, the most common mutations were c.C301T (p.R101W) and c.G537A (p.T179T). Patient characteristics included extremely early onset of symptoms and extra-intestinal manifestations such as recurrent perianal lesions, oral ulcers, and skin rashes, which were common. UCBT and thalidomide might be effective treatments, although the mortality rate was high in this study.

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An Analysis and Survey on Interleukin-10 Receptor Mutation in Inflammatory Bowel Disease in Iranian IBD Cohort

Advances in Bioengineering and Biomedical Science Research ◽

10.33140/abbsr/02/01/00003 ◽

2019 ◽

Vol 2 (1) ◽

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Early Onset ◽

Pcr Amplification ◽

Interleukin 10 ◽

Genes Encoding ◽

Healthy Control ◽

Inflammatory Bowel ◽

Total Dna

Background: Early-onset inflammatory bowel disease (IBD) is classified to Crohn’s disease, ulcerative colitis and unclassified disorders which have chronic, relapsing course and can result in substantial long-term morbidity. IBD is a multifactorial disorder with genetic susceptibility, immunological predisposition and environmental triggers. Objective: To generally determine prevalence of IL10R mutation in IBD patients in Iran-Isfahan, we performed sequencing of all exons in IL10RA and IL10RB in cohort of IBD patients and healthy control. Material and Method: Total DNA content of 76 patients and 50 healthy controls were extracted from whole blood and PCR amplification and sequencing was done. Result: Overall identified IL-10RA mutations were P.(I224V), P.(A153V), P.(A153A), P.(S159G), P.(R263Q), P.(R284C), P.(R351Q), P.(Q376Q), P.(T416I), P.(A493V), P.(A511A) and P.(S563S). In IL10RB gene the only detected mutation was P. (K47E). Of them, P.(A153V), P.(A153A), P.(R284C), P.(T416I), P.(A493V), P.(A511A), P.(S563S) were Not reported variant in IBD variants. Conclusion: Our results also confirmed that early-onset IBD could be attributed to a synergistic effect of several variant alleles of the genes encoding IL10 receptors. These variants, alone, could only give rise to a sub-clinical manifestation of the IBD.

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

10.21203/rs.3.rs-34174/v1 ◽

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.

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