Tcf4 in gut development; investigating underlying causes of gastro-intestinal problems in patients with Pitt Hopkins syndrome
Awardee: Simone Mesman
Institution: University of Amsterdam
Grant Amount: $58,602
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Many patients with Pitt Hopkins syndrome (PTHS) experience serious gastro-intestinal (GI) problems, like severe abdominal bloating and constipation. Recently, two patients in the Netherlands unexpectedly passed away due to GI complications, underlining the need to thoroughly understand these problems in order to develop better treatment. Although these GI problems have a large influence on the quality of life of patients with PTHS and their caregivers, very little research has been done to determine the underlying causes of these problems. With the current project we aim to shed light on the possible cause(s) of the the GI problems and possible therapeutic strategies to alleviate (some of) these problems. To this end we will investigate the role of Tcf4 in gut development in patients with PTHS and in specific mouse models carrying Tcf4 mutations. To determine whether Tcf4 functions in the gut or in gut development, we will examine the normal expression pattern of Tcf4 in the human and murine gut. Next to this we will investigate the cellular and molecular architecture of the gut in patients with PTHS and mice carrying specific Tcf4 mutations. Furthermore, we will study co-morbidity of GI problems with other PTHS symptoms to determine whether specific symptoms may be related to each other. Taken together, the results from this study will help us identify the underlying causes of GI problems in patients with PTHS and pinpoint possible therapeutic targets. Furthermore, it will help us fine-tune existing treatments specifically aimed to alleviate GI problems in PTHS.