Identification of a Novel Pathogenic LDLR Mutation in a Chinese Family with Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) as the most common risk factor for premature coronary artery disease (CAD), results in huge economic burden on families and society, but it could be significantly under-diagnosed. Methods: : In this study, we identified a pathogenic frame shift insertion mutation in LDLR (c.2517_2518insCA, p.C839fs) from a Chinese FH family through whole exome sequencing (WES) and sanger sequencing, which hasn't been reported before. According to the 2015 ACMG/AMP, the nonsense pathogenic mutation on LDLR (c.2517_2518insCA, p.C839fs) was classified as “pathogenic”. Results: : This LOF mutation was estimated to change the free energy dynamic of RNA molecule, thus its stability and protein structure were predicted to eliminate an essential LDLR functional domain. Conclusions: : This finding expanded our understanding of Phenotype–Genotype correlations of FH with LDLR gene mutations and emphasized the important role of genetic testing and genetic screening in the diagnosis and intervention of FH.