Novel genes found in inflammatory bowel disease under age 5

September 3, 2015, Children's Hospital of Philadelphia
Judith R. Kelsen, M.D., is a pediatric gastroenterologist at The Children's Hospital of Philadelphia. Credit: The Children's Hospital of Philadelphia

Researchers analyzing the complicated genetic influences in inflammatory bowel disease have discovered new gene variants associated with an often-severe type of the disease that affects children under age five. The genes play important roles in immune function, and that knowledge helps guide more precise, individualized treatments for very young patients.

"As we continue to understand the specific functions of these genes in this type of childhood-onset disease, we are working to design more effective therapies," said study leader Judith R. Kelsen, M.D., a pediatric gastroenterologist in the Center for Pediatric Inflammatory Bowel Disease at The Children's Hospital of Philadelphia (CHOP).

Kelsen and colleagues published their findings July 16 online in the journal Gastroenterology.

Inflammatory bowel disease (IBD) is a painful, chronic inflammation of the gastrointestinal tract, affecting roughly two million children and adults in the U.S. IBD beginning in childhood tends to be more severe than adult-onset disease. In fact, very early-onset IBD (VEO-IBD), diagnosed under age five, is often more severe than IBD that starts later in childhood, and often more challenging to treat. Kelsen specializes in caring for children with VEO-IBD.

"There has been extensive research in the genes contributing to adult-onset IBD and in children aged 10 and older," said Kelsen, "but relatively little research has been performed in the very-early onset subtype of the disease." Furthermore, she added, much of the previous work relied on genome-wide association studies (GWAS), which often do not find rare gene variants. The current study used newer technology, whole exome sequencing, which has revolutionized the ability to study .

The study team analyzed DNA from 125 children with VEO-IBD, all of them under age four, along with DNA from 19 of their parents. A control group of 210 subjects included 145 healthy individuals, 45 patients with pediatric IBD and 20 with adult-onset Crohn's disease (one of the two major types of IBD).

Because IBD is a complex disease, in which a patient's genes may alter immune response to environmental exposure, the researchers focused on specific genes or biological pathways associated with primary immunodeficiency disorders.

The researchers found rare and novel variants in genes that regulate B-cells and T-cells—immune cells with important roles in immunodeficiency disorders. They also discovered rare variants in the IL10RA gene, a member of a key pathway. "Our findings reinforce other research that has revealed considerable overlap among involved in different immune-related diseases," said Kelsen. "This overlap is reflected in the fact that VEO-IBD may be a form of primary immunodeficiency." She added that she expects further whole-exome studies to identify additional immune-related gene variants and pathways.

Kelsen and one of her co-authors, Kathleen E. Sullivan, M.D., Ph.D., chief of Immunology at CHOP, run a joint immunology/IBD clinic once a month for children with VEO-IBD.

For health providers caring for children with VEO-IBD, said Kelsen, the research underlines the importance of doing complete immunological workups for these patients, in addition to IBD evaluations. Sometimes, she noted, a genetic workup may also be necessary. "Evaluation and treatment guidelines are not yet standardized for with very early-onset IBD, but we have found that this subtype of IBD is somewhat different from IBD that begins later. As we better understand the specific components of the immune system that may be involved in this , clinicians will be better prepared to individualize treatment to each patient."

Funds from the National Institutes of Health (grant K23DK100461-01A1) supported this research. Kelsen's and Sullivan's co-authors at CHOP included Noor Dawany, Ph.D., David Piccoli, M.D., Petar Mamula, M.D., Robert N. Baldassano, M.D., and Marcella Devoto, Ph.D.

Explore further: Chronic narcotic use is high among kids with IBD

More information: "Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients with Very Early Onset Inflammatory Bowel Disease," Gastroenterology, published online July 17, 2015.

Related Stories

Chronic narcotic use is high among kids with IBD

February 9, 2015
Chronic narcotic use is more than twice as prevalent in children with inflammatory bowel disease (IBD), compared with children without this disease, according to a new study published in Clinical Gastroenterology and Hepatology, ...

Comprehensive study of genetic risks for inflammatory bowel disease in African-Americans

August 25, 2015
Researchers at the Johns Hopkins University School of Medicine, along with colleagues at Emory University and Cedars-Sinai, have published in the journal Gastroenterology the first major, in-depth analysis of genetic risk ...

Improving lymphatic function protects mice from experimental colitis

August 8, 2014
Chronic inflammatory bowel disease can be painful and debilitating. Both genetics and environment are thought to promote disease, but it is not fully understood how chronic IBD develops. Emerging evidence indicates that IBD ...

Female IBD patients: Stay up-to-date on your cervical cancer screening

March 26, 2015
Women with inflammatory bowel disease (IBD) may be at increased risk of cervical dysplasia and cancer, according to a new study published in Clinical Gastroenterology and Hepatology, the official clinical practice journal ...

Generalized anxiety disorders twice as likely in those with inflammatory bowel disease

July 29, 2015
People who have inflammatory bowel disease (IBD), such as Crohn's disease or ulcerative colitis, have twice the odds of having a generalized anxiety disorder at some point in their lives when compared to peers without IBD, ...

Younger immigrants at higher risk of developing inflammatory bowel disease

March 10, 2015
The younger a person is when they immigrate to Canada, the higher their risk of developing inflammatory bowel disease (IBD), and its major subtypes Crohn's disease and ulcerative colitis, according to a study by researchers ...

Recommended for you

New osteoarthritis genes discovered

March 19, 2018
In the largest study of its kind, nine novel genes for osteoarthritis have been discovered by scientists from the Wellcome Sanger Institute and their collaborators. Results of the study, published today (19 March) in Nature ...

Scientists discover how gene mutation reduces the need for sleep

March 19, 2018
It's every over-achiever's dream: a gene mutation that allows them to function normally with just four to six hours of sleep a night instead of the normal eight.

At-home genetic testing leads to misinterpretations of results

March 19, 2018
Home genetic tests like AncestryDNA and 23andMe are more popular than ever, with sales topping $99 million in 2017. But a new study led by a Boston University School of Public Health researcher highlights the potential negative ...

New methods find undiagnosed genetic diseases in electronic health records

March 15, 2018
Patients diagnosed with heart failure, stroke, infertility and kidney failure could actually be suffering from rare and undiagnosed genetic diseases.

Hundreds of genes linked to intelligence in global study

March 14, 2018
More than 500 genes linked to intelligence have been identified in the largest study of its kind. Scientists compared variation in DNA in more than 240,000 people from around the world, to discover which genes are associated ...

Study finds that genes play a role in empathy

March 12, 2018
A new study published today suggests that how empathic we are is not just a result of our upbringing and experience but also partly a result of our genes.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.