Gain-of-function variants in SMAD4 compromise respiratory epithelial function.

ABSTRACT:

Background

Myhre syndrome is an exceedingly rare yet increasingly diagnosed genetic disorder arising from germline variants in the SMAD4 gene. Its core manifestation is the progression of stiffness and fibrosis across multiple organs. Individuals with Myhre syndrome exhibit a propensity for upper respiratory tract remodeling and infections. The molecular and cellular mechanisms underlying this phenotype remain unclear.

Objective

We sought to investigate how SMAD4 pathogenic variants associated with Myhre syndrome affect SMAD4 protein levels, activation, and physiological functions in patient-derived nasal epithelial cells.

Methods

Clinical observations were conducted on a cohort of 47 patients recruited at Massachusetts General Hospital from 2016 to 2023. Nasal epithe

SUBMITTER: Lindsay ME 

PROVIDER: S-EPMC11700783 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature