Gain-of-function Variants in SMAD4 compromise Respiratory Epithelial cells

To investigate how SMAD4 mutations associated with Myhre syndrome impact SMAD4 protein levels, activation and physiological functions in patient derived nasal epithelial cells. We derived primary nasal basal stem cells from inferior turbinate brushings of healthy subjects and Myhre syndrome patients (SMAD4-Ile500Val, Arg496Cys, Ile500Thr). After ALI differentiation, RNA was collected from healthy nasal basal epithelial cells and Myhre syndrome-epithelial cells to perform mRNA Deep sequencing. We then performed gene expression profiling analysis using data obtained from RNA-seq. Overall design: Total RNA was extracted from nasal basal epithelial cells (passage P1). Comparative gene expression profiling analysis was done of RNA-seq data for nasal basal epithelial cells and Myhre syndrome-epithelial cells.