Functional analysis of <i>FH</i> variants of uncertain significance using <i>Caenorhabditis elegans</i> model.

ABSTRACT:

Purpose

Variants of uncertain significance (VUS) in the essential metabolic gene fumarase (FH) have hampered diagnosis for patients with FH-associated diseases. Yet, early intervention is crucial for disease management, making the accurate and timely interpretation of VUS a clinical priority. Utilizing the multicellular model Caenorhabditis elegans (C. elegans), with a highly conserved fumarase ortholog (FUM-1), we aimed to facilitate functional analysis and interpretation of clinical FH variants.

Methods

We used CRISPR-Cas9 techniques to generate C. elegans strains homozygous for FH variants reported in ClinVar and then assessed the effects on the animal's development.

Results

C. elegans strains homozygous for a

SUBMITTER: Ferris S 

PROVIDER: S-EPMC12719760 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature