Genetic Mutations Behind Very-Early-Onset-Inflammatory Bowel Disease Explored

A genetic mutation lies behind the development of Very-Early-Onset-Inflammatory Bowel Disease in children, found researchers from Johns Hopkins Medicine.

Inflammatory bowel disease (IBD) refers to disorders that involve chronic inflammation of your digestive tract. They occur due to multiple genetic mutations and environmental factors, including diet, pollution, and an imbalance in the gut microbiota. These things cause immune cells in the intestines to get over-activated and cause inflammation in the gut.

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Inflammatory bowel disease involves chronic inflammation of the colon and small intestine. Symptoms include diarrhea, abdominal pain and weight loss.

‘MDA5 proteins fight against viruses that invade the gut. When mutations occur in the gene that produces this protein, the improperly activated immune cells trigger inflammation and lead to Very-Early-Onset-Inflammatory Bowel Disease.’

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Globally, four out of every 100,000 births develop Very-Early-Onset-Inflammatory Bowel Disease. Unlike other IBDs, this condition is diagnosed in children before the age of six.

The researchers of the current study aimed to see if children have a greater genetic susceptibility for this type of inflammatory bowel disease because they develop it so young.

For this, they collected tissue samples from 24 patients with Very-Early-Onset-Inflammatory Bowel Disease and performed whole-exome sequencing that looks for mutations in the protein-producing areas of a gene. The team then made use of the online database called GeneMatcher that contains genetic variations from people worldwide.

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These steps showed that eight people with the inflammatory condition had nine unique mutations in parts of a gene called IFIH1. This gene is involved in the production of a protein called MDA5 that helps fight against viral infections in the gut.

In each patient with the IFIH1 mutation, the MDA5 proteins only partially worked, giving rise to improper activation of the immune system that could trigger the inflammation that leads to Very-Early-Onset-Inflammatory Bowel Disease.

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“When you look at the physical changes associated with IFIH1 mutations, there is a wide range, and they are really very different. It’s crucial to know that these different variations in the same gene can cause these different characteristics,” said Dr. Nara Sobreira, assistant professor of genetics and pediatrics at the Johns Hopkins University of Medicine and co-founder of GeneMatcher.

The team hopes their findings will provide some new insights for clinicians to pinpoint the genetic cause of the disease and inform treatment options to the patients. The work was supported by a grant from the National Human Genome Research Institute and funding from the Intramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Source-Medindia