Imaging flow cytometry-based cellular screening elucidates pathophysiology in individuals with Variants of Uncertain Significance.

ABSTRACT:

Background

Deciphering variants of uncertain significance (VUS) represents a major diagnostic challenge, partially due to the lack of easy-to-use and versatile cellular readouts that aid the interpretation of pathogenicity and pathophysiology. To address this challenge, we propose a high-throughput screening of cellular functionality through an imaging flow cytometry (IFC)-based platform.

Methods

Six assays to evaluate autophagic-, lysosomal-, Golgi- health, mitochondrial function, ER stress, and NF-κβ activity were developed in fibroblasts. Assay sensitivity was verified with compounds (N = 5) and positive control patients (N = 6). Eight healthy controls and 20 individuals with VUS were screened.

Results

All molecular compounds and positive controls showed significan

SUBMITTER: Muffels IJJ 

PROVIDER: S-EPMC11806768 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature