Variability in proliferative and migratory defects in Hirschsprung disease-associated <i>RET</i> pathogenic variants.

ABSTRACT: Despite the extensive genetic heterogeneity of Hirschsprung disease (HSCR; congenital colonic aganglionosis) 72% of patients harbor pathogenic variants in 10 genes that form a gene regulatory network (GRN) controlling the development of the enteric nervous system (ENS). Among these genes, the receptor tyrosine kinase gene RET is the most significant contributor, accounting for pathogenic variants in 12%-50% of patients depending on phenotype. RET plays a critical role in the proliferation and migration of ENS precursors, and defects in these processes lead to HSCR. However, despite the gene's importance in HSCR, the functional consequences of RET pathogenic variants and their mechanism of disease remain poorly understood. To address this, we investigated the proliferative and migratory phe

SUBMITTER: Fries LE 

PROVIDER: S-EPMC11451626 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature