However, 3% of patients in Munich with a clinical diagnosis of FH have a particular mutation in the apolipoprotein B gene causing familial defective apolipoprotein B-100 (FDB).
Effect of apolipoprotein E polymorphism and XbaI polymorphism of apolipoprotein B on response to lovastatin treatment in familial and non-familial hypercholesterolaemia.
Subjects with non-familial hypercholesterolemia who were homozygous for absence of an XbaI restriction site in the apolipoprotein B gene (genotype X2X2) had significantly lower values of apolipoprotein B than those possessing the site.
These studies have defined the variables affecting neonatal ApoB levels and establish that neonatal screening for familial hypercholesterolaemia is feasible.
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.
By direct comparison of the Lp(a) and apoB plasma concentrations in 28 affected and 31 unaffected members of seven families carrying the FH trait and without history of coronary artery disease, we reached the conclusion that LDL receptor activity is not a major determinant of the Lp(a) plasma levels in these subjects.
An investigation of the influence of selected factors on the clinical expression of the FH Afrikaner-1 mutation in this family indicated that it was especially the elevated apolipoprotein (a) levels, in addition to low levels of high density lipoprotein cholesterol and raised triglyceride and apolipoprotein B levels, that were associated with a greater risk of developing CHD.
Mutations in the LDL receptor (LDLR) gene and the codon 3500 region of the apolipoprotein (apo) B-100 gene result in the clinically indistinguishable phenotypes designated familial hypercholesterolemia (FH) and familial defective apo B-100 (FDB), respectively.
A total of 357 hypercholesterolaemic patients, 48 with a clinical diagnosis of familial hypercholesterolaemia attending lipid clinics in Scotland and Wales, were screened for the presence of FDB.
Hypercholesterolemia clustering in families not explained by either low density lipoprotein (LDL)-receptor mutations producing familial hypercholesterolemia (FH), or the apolipoprotein B (apo B) Arg3500-->Gln mutation with familial defective apo B (FDB), is common in the Finnish population.
These data show that the in vivo metabolism of apo B-100-containing lipoproteins in FDB is different from that in familial hypercholesterolemia, in which LDL receptors are defective.
The surprising result that only two mutations of apoB in the receptor-binding domain (Arg 3500 Gln and Arg 3531 Cys) were associated with defective LDL binding, hypercholesterolemia, or CAD is in stark contrast with familial hypercholesterolemia, where nearly 150 mutations of the LDL receptor have been described that disrupt its function.
Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine.
Evaluation of a clinically applicable mutation screening technique for genetic diagnosis of familial hypercholesterolemia and familial defective apolipoprotein B.
To evaluate if this may be caused by other hitherto undescribed genetic defects or to failure of the functional assays, we undertook denaturing gradient gel electrophoresis based mutation screening of the LDLR gene and the codon 3456 3553 region of the apolipoprotein B gene in six French FH/FDB patients with normal outcomes on functional assays.
Monogenically inherited hypercholesterolemia is most commonly caused by mutations at the low density lipoprotein receptor (LDLR) locus causing familial hypercholesterolemia (FH) or at the apolipoprotein B (APOB) locus causing the disorder familial defective apoB (FDB).
The five most common LDL receptor mutations in Danish patients with familial hypercholesterolemia and three mutations in the apolipoprotein B gene did not predispose to ischemic cerebrovascular disease of the young.
Sibpair studies in families including familial defective apolipoprotein B or familial hypercholesterolemia (FH) heterozygotes have demonstrated that, in addition, mutations in apolipoprotein B and in the LDL receptor (LDL-R) gene may affect Lp(a) plasma concentrations, but this issue is controversial.