Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.

Abstract

Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG----CAG), a CG mutational "hot spot," defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia.

Molecular Characterization of Iranian Patients with Possible Familial Hypercholesterolemia

“…The latter situation usually results in a mild or severe form of hypercholesterolemia together with an increased risk for early onset atherosclerosis [10,11]. In contrast to LDLR, only a small number of functional mutations have been identified in APOB gene such as R3500Q [12], R3500 W [13], and R3531C [14]. There are very limited data regarding LDLR and APOB gene mutations in Iranian population [15,16].…”

Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals

“…APOB mutations have been estimated to account for 1-5% of patients with FH, and are inherited in an autosomal dominant manner [65,66]. From APOB, apo B-100 is synthesized exclusively in the liver as one of the two main protein isoforms, and is a major constituent of LDL and VLDL.…”

Identification of three mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians

“…All these children were negative for the six previously known FC Mutations in the LDL receptor gene (Simard et al, 1994) and were then screened for the three mutations. The ApoB 3500 mutation (Soria et al, 1989) was not found in any of the 15 adult FH patients or in any of the 48 children, as determined by the assay that was previously described (Hansen et al, 1991). Additional 100 normocholesterolemic FC men were also screened for the C152W and C347R mutations in order to exclude that these mutations are not linked polymorphisms.…”