Identification of Highly Penetrant Mutation in Immune Mediated Disease

Immune Mediated Diseases (IMDs) are caused by an abnormal inflammatory response, leading to tissue damage in one or more organs. Examples include Crohn’s disease, juvenile idiopathic arthritis (JIA), and rarer diseases such as primary immunodeficiencies. Other IMDs defy categorization and are labeled as “undiagnosed disease”, an evolving concept in clinical care. Treatment of any of these diseases involves suppressing the immune system, which carries a risk of opportunistic infection, malignancy, and possibly death. The majority of IMDs are incurable and their cause(s) remain largely unknown.

In clinical practice, Stephen Guthery, MD, and his team treat children with undiagnosed IMDs, which are often multi-systemic and life-threatening. In search of a diagnosis, the researchers are sequencing the genomic DNA of three patients with highly unusual IMDs. As part of this investigation, the scientists will follow up on preliminary data that suggests a candidate gene for one of these patients.

Guthery and his team are also investigating the genetic causes of known IMDs. They are mining the Utah Population Database for families with inheritance patterns of Crohn’s disease, ulcerative colitis, JIA, or multiple IMDs. Once identified, they will sequence the DNA of multiple families to find responsible genetic variants. A better understanding of the genetics of IMDs will provide valuable insight into these devastating diseases, potentially leading to improved treatments and outcomes.

Listen to an interview with Stephen Guthery on The Scope Radio.

Ulcerative colitis

Ulcerative colitis, an immune mediated disease (IMD). Endoscopic image of a bowel section known as the sigmoid colon afflicted with ulcerative colitis. The internal surface of the colon is blotchy and broken in places.