Independent mutation of arginine((3500)) → glutamine associated with familial defective apolipoprotein B-100

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. It is postulated that FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apoB gene creating a substitution of glutamine for arginine in amino acid 3500. The arginine((3500)) → glutamine mutation has been identified on the same haplotype of the apoB gene in several populations from North America and Europe, suggesting that it occurred on a single ancestral gene. Independent mutations were not observed. The purpose of this paper is to report on a family where individuals show a dominantly inherited increase of plasma LDL associated with an independent arginine((3500)) → glutamine mutation as determined by haplotype analysis using polymorphic markers of the apoB gene. The identification of these individuals is strong evidence that the arginine((3500)) → glutamine mutation is causative for the defective binding of apoB-100.