De Novo GUCY2C and PRR12 Mutations in a Patient With Chronic Diarrhea, Small Bowel Obstructions, and Developmental Delay

We present the case of a 30-year-old man with a history of neurodevelopmental delay and congenital secretory diarrhea since childhood complicated by recurrent small bowel obstructions requiring multiple surgeries. Genetic testing identified a de novo gain-of-function GUCY2C c.2309T>C (p.Leu770Pro) mutation, causing congenital diarrhea through persistent chloride and water secretion in a mechanism similar of enterotoxigenic E. coli. For less clear reasons, the mutation is also associated with small bowel obstructions and Crohn's disease-like phenotype. A co-occurring de novo PRR12 c.768del (p.Ala257Leufs*58) frameshift mutation explained his developmental delay. Together, these findings resolved a decades-long diagnostic challenge and enabled a personalized care plan for the patient.