First, the LDLR locus was expressed appropriately in the ldl(-/-)a7 Chinese hamster ovary (CHO) cell line immediately following infectious delivery; second, the locus was maintained within a replicating episomal vector and expressed at broadly physiological levels in CHO cells for 3 months following infectious delivery; and third, the locus was efficiently expressed in human fibroblasts derived from FH patients.
We recognized a 45-year-old Saudi female FH patient with double variants in the LDLR [c.1255 T > G, p.(Y419D)] and LDLRAP1 genes [c.604_605delTCinsA, p.(S202Tfs*2)].
Median 125I-LDL association levels in these groups appeared to be in agreement with hypothesis that two different geno-types in HC heterozygotes and three in non-HCs determined LDL receptor activity.
The study was performed with 70 carriers of two LDL-receptor mutations common in northern Italy (i.e., the 4 bp insertion in exon 10 known as FH-Savona and the D200G missense mutation in the exon 4, known as FH-Padova 1) and 100 healthy controls.
For instance, the use of novel techniques to detect copy number variations, such as multiplex ligation-dependent probe amplification, has revealed many additional causative mutations in the low-density lipoprotein receptor gene in patients with familial hypercholesterolemia.
Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly "humanized" mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH.
The finding of a compound heterozygous mutation causing severe FH phenotype is important for the genotype-phenotype correlation and also enlarges the spectrum of FH-causative LDLR variants in the Arab population, including the Saudi population.
By applying this approach to missense alleles identified through cohort-level exome sequencing in the low-density lipoprotein receptor (LDLR) we are able to distinguish rare alleles that predispose to familial hypercholesterolemia and myocardial infarction from alleles without obvious impact on LDLR levels or functions.
Increasing the sensitivity of single-strand conformation polymorphism analysis of the LDLR gene mutations in brazilian patients with familial hypercholesterolemia.
We showed an age-related gene-dosage effect of deletion of the low-density lipoprotein receptor (LDL-R) gene on aortic calcification in human subjects with FH.
A patient with clinical phenotype of homozygous FH and her parents were investigated for mutations in the promoter and all eighteen exons of the LDL-R gene.
In a previous study, we have shown that in patients with definite FH around 20% had no identifiable gene defect after screening the entire exon coding area of the low density lipoprotein receptor (LDLR) and testing for the common Apolipoprotein B (ApoB) R3500Q mutation.