Characterisation of mutatations in the TTC7A gene associated with Very Early Onset of Inflammatory Bowel Disease

Abstract

The lining of our guts is made up of epithelial cells that create a barrier which prevents the spilling of intestinal contents into the rest of the body. Breakages in this epithelial barrier can lead to digestive problems and infection. Such barrier abnormalities accompanied with inflammation, often fatal, have been found in newborns and young children diagnosed with different diseases of the intestines and immune system. As a consequence, the gene TTC7A has been identified as a potential source for those abnormalities. The role of TTC7A in the maintenance of the epithelial barrier and in immune cells is not well-understood and therefore a cure does not exist. To address this gap in knowledge, we used small models of the gut, called organoids, taken from patients with TTC7A disease. Our organoids reflected the various epithelial defects observed in patients. We discovered novel interactions of TTC7A with other genes and their products responsible for cellular structure, and identified a drug that can help restore the function of the epithelial barrier. Our testing model can be used as a diagnostic tool to characterise epithelial abnormalities in patients and to test their responsiveness to a range of drugs.