Pathogenic LDLR Variants (c.103 C>T and c.2416dup) in ligand-binding and cytosolic domains in Saudi familial hypercholesterolemia: Molecular characterization and computational insights.

ABSTRACT: Familial hypercholesterolemia (FH) results in elevated levels of LDL-C, increasing the risk of developing cardiovascular disease. This study aims to identify genetic causes and examine the connection between genetic variants and the resulting genotype-protein phenotype in Saudi FH patients. Whole-exome sequencing (WES) and Sanger sequencing were employed to detect causative variants in affected Saudi FH families and their healthy relatives. Computational tools, including RNA stability analysis, molecular dynamics simulations, and molecular docking were used to assess the impact of these variants on mRNA stability and protein structure, particularly LDLR-LDLRAP1 interactions. WES identified two pathogenic variants in the LDLR gene in two Saudi FH families: c.103 C>T p.(Gln35Ter) and c.2416d

SUBMITTER: Al Mahdi HB 

PROVIDER: S-EPMC12447921 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature