Work

Novel homozygous nonsense mutation in glucagon‐like peptide‐2 receptor gene resulting in severe human illness

Year: 2024

Type: article

Abstract: Glucagon-like peptide-2 (GLP2) acts on the GLP2 receptor (GLP2R) and plays a role in intestinal growth and adaptation. The endogenous actions of GLP2R do not have an established association with human disease, although mouse-knockout models in a stressed state show enhanced susceptibility to small bowel injury, increased morbidity, mortality, and abnormal host-bacterial interactions. We report an 11-month-old female with multiple intensive care unit admissions for severe metabolic acidosis due to profuse nonbloody diarrhea in the context of various infections. She had normal growth, lab testing, and stooling patterns between illnesses. Trio-whole genome sequencing revealed homozygous nonsense variants resulting in nonfunctional GLP2R. This is the first known human documented with a GLP2R-deficient phenotype, resulting in clinical illness, which correlates with the findings in the GLP2R mouse knockout model and furthers our understanding of GLP2R and the action of teduglutide, a GLP2 analog used for the treatment of short bowel syndrome.

Source: JPGN Reports

DOI: 10.1002/jpr3.12125

Authors: Claire Jaramishian, Shivani Kamal, Martín G. Martín, Nathan Zev Minkoff

Institutions: Children's Hospital Central California, University of California, Los Angeles, Mattel Children's Hospital

Language: English

Topic: Clinical Nutrition and Gastroenterology

Subfield: Nutrition and Dietetics

Field: Nursing

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $1,900