However, the elevation of plasma low-density lipoprotein cholesterol observed in FDB is frequently milder than that of FH due to mutations in LDLR, and FDB is subsequently underdiagnosed according to standard FH diagnostic criteria.
Mutations within the LDL receptor and/or apolipoprotein B-100 genes compromising this process may lead to congenital monogenic hypercholesterolaemias known as familial hypercholesterolaemia or familial defective apolipoprotein B-100.
Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred.
Familial defective apolipoprotein B-100 (FDB) is a genetic disorder characterized by a decreased binding of low-density lipoprotein (LDL) particles to the LDL receptor due to defective apo B-100.
By screening two groups of probands, clinically diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and 305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively).
Existence of both FH and FDB should be considered in families with LDL-receptor mutations in some but not all individuals with hypercholesterolemia or when some individuals in families with FH exhibit exaggerated hypercholesterolemia.
Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.
Autosomal dominant type IIa hypercholesterolemia: evaluation of the respective contributions of LDLR and APOB gene defects as well as a third major group of defects.
A cohort of 236 apparently unrelated patients with clinical features of FH was screened for a common mutation causing familial defective apolipoprotein B-100 (FDB) and seven low-density lipoprotein receptor (LDLR) gene defects known to be relatively common in South Africans with FH.
Mutations in the LDL receptor (LDLR) or the apolipoprotein B-100 genes causing familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB), two of the most frequent inherited diseases, are the underlying genetic defects in a small proportion of patients suffering from premature atherosclerotic heart disease.
Patients with LDLR defects had a significantly higher risk of myocardial infarction, coronary artery bypass graft, positive coronary angiography, atherosclerotic plaques in the carotid arteries and CAD (p<0.01) than patients with FDB.
The LDL of FDB heterozygotes had 40% (n = 10) the affinity of normal LDL (n = 12) for the LDL receptor on cultured fibroblasts, and 55% (n = 6) of normal LDL (n = 6) for that on HepG2 cells.
In probands, segregation analysis complemented by DNA sequencing identified heterozygous defective alleles and mutations on two nonallelic loci for two monogenic lipid disorders: familial hypercholesterolemia at the low density lipoprotein (LDL) receptor locus and familial defective apolipoprotein B-100 at the locus encoding its ligand, apolipoprotein B-100.
The affinity of low-density lipoproteins and of very-low-density lipoprotein remnants for the low-density lipoprotein receptor in homozygous familial defective apolipoprotein B-100.
Although, hypercholesterolaemia segregated with haplotypes both at the apolipoprotein B and low density lipoprotein (LDL) receptor loci in the proband's family, LDL receptor analysis revealed that the proband was not doubly heterozygous for FDB and FH.
Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder characterized by decreased binding of low density lipoprotein (LDL) to the LDL receptor due to a substitution of glutamine for arginine in residue 3500 of apolipoprotein B-100.
Familial defective apolipoprotein B-100 (FDB) is caused by a single G-to-A substitution at nucleotide 10,708 leading to an arginine to glutamine change at amino acid 3,500 of the apolipoprotein B-100 and thus, a reduced binding of the apolipoprotein B to the low density lipoprotein (LDL) receptor.
Frostegård et al.(J Lipid Res 1990;31:37-44) demonstrated that the proliferation of the human monocyte cell line U937 is critically dependent on the uptake of low-density lipoprotein (LDL) via the apo B, E (LDL) receptor, a characteristic that was used to detect patients with familial defective apolipoprotein B-100 (FDB).
Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor.
Familial defective apolipoprotein B-100 (FDB) is characterized by a decreased affinity of low density lipoprotein (LDL) to the LDL receptor resulting in a dominantly inherited increase of plasma LDL.