Detection of MEFV Gene Mutations in Patients with Inflammatory Bowel Disease

Background. The clinical and pathological features of inflammatory bowel disease (IBD) and Familial Mediterranean Fever (FMF) are similar. Objective. Here, the frequency of Mediterranean Fever (MEFV) gene mutation and its effect on the outcome of IBD were evaluated. Methods. DNA sequence analysis detected the variants on the MEFV gene in patients with IBD. The relationship between mutations and the need for steroids, immunomodulators, biologics, and surgery was assessed. Results. We evaluated 100 patients with IBD (55 with ulcerative colitis (UC) and 45 with Crohn’s disease (CD)) and 60 healthy individuals as controls. The frequency of MEFV gene mutation was 26.7% ( n = 12 ) and 14.5% ( n = 8 ) for UC and CD, respectively. No relationship was found between MEFV gene mutation and the need for steroids, immunomodulators, and biologics ( p = 0.446 ; p = 0.708 ; p > 0.999 , resp.); however, in UC, the need for surgery in those with mutation ( p = 0.018 ) and E148Q mutation alone was significant ( p = 0.037 ). Conclusion. The rate of MEFV gene mutations was high in patients with UC who required surgery. These patients have frequent and severe attacks, indicating that the mutations are related to disease severity. MEFV mutation as a modifier factor of IBD should be considered.

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MEFV Gene-Related Enterocolitis Account for Some Cases Diagnosed as Inflammatory Bowel Disease Unclassified

Digestion ◽

10.1159/000502640 ◽

2019 ◽

Vol 101 (6) ◽

pp. 785-793 ◽

Cited By ~ 2

Author(s):

Daisuke Saito ◽

Noritaka Hibi ◽

Ryo Ozaki ◽

Oki Kikuchi ◽

Taro Sato ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gene Mutation ◽

Bowel Disease ◽

Periodic Fever ◽

Mefv Gene ◽

Clinical Manifestations ◽

Gene Mutations ◽

University Hospital ◽

Mucosal Inflammation ◽

Inflammatory Bowel

Background and Aims: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. Methods: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. Results: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26–76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. Conclusions: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

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The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease

Gastroenterology ◽

10.1053/gast.2002.32415 ◽

2002 ◽

Vol 122 (4) ◽

pp. 867-874 ◽

Cited By ~ 454

Author(s):

Andrew P. Cuthbert ◽

Sheila A. Fisher ◽

Muddassar M. Mirza ◽

Kathy King ◽

Jochen Hampe ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gene Mutations ◽

Inflammatory Bowel

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Association of the MEFV Gene Variations With Inflammatory Bowel Disease in Turkey

Journal of Clinical Gastroenterology ◽

10.1097/mcg.0b013e3182597992 ◽

2013 ◽

Vol 47 (3) ◽

pp. e23-e27 ◽

Cited By ~ 24

Author(s):

Filiz Akyuz ◽

Fatih Besisik ◽

Duran Ustek ◽

Cumhur Ekmekçi ◽

Aytul Uyar ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Mefv Gene ◽

Inflammatory Bowel

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Clinical phenotypes and genotypic characteristics of infantile-onset inflammatory bowel disease with interleukin-10 receptor A mutations in 22 Chinese children

10.21203/rs.3.rs-34174/v2 ◽

2020 ◽

Author(s):

Dexiu Guan ◽

Jing Zhang ◽

Shu Guo ◽

Feihong Yu ◽

Jin Zhou ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mortality Rate ◽

Bowel Disease ◽

Early Onset ◽

Gene Mutations ◽

Interleukin 10 ◽

Clinical Phenotypes ◽

Oral Ulcers ◽

Inflammatory Bowel ◽

Genotypic Characteristics

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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NOD2 gene mutations associate weakly with ulcerative colitis but not with Crohn's disease in Indian patients with inflammatory bowel disease

Gene ◽

10.1016/j.gene.2012.10.015 ◽

2013 ◽

Vol 512 (2) ◽

pp. 309-313 ◽

Cited By ~ 16

Author(s):

Srinivasan Pugazhendhi ◽

Srikanth Santhanam ◽

Jayanthi Venkataraman ◽

Isabelle Creveaux ◽

Balakrishnan S. Ramakrishna

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Gene Mutations ◽

Indian Patients ◽

Inflammatory Bowel

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Association of IRGM Gene Mutations with Inflammatory Bowel Disease in the Indian Population

PLoS ONE ◽

10.1371/journal.pone.0106863 ◽

2014 ◽

Vol 9 (9) ◽

pp. e106863 ◽

Cited By ~ 14

Author(s):

Kirankumar Baskaran ◽

Srinivasan Pugazhendhi ◽

Balakrishnan S. Ramakrishna

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Indian Population ◽

Gene Mutations ◽

Inflammatory Bowel

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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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