A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the Msp I site around codon 4046 in exon 29 of the APOB gene. Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced. The mutation was a C to T transition, substituting tryptophan for arginine at amino acid position 4019 of the mature ApoB-100 protein. Seven relatives of the proband had the same mutation, which has been called "ApoB-100 Hopkins." Only three of seven relatives with the mutation had hyperapobetalipoproteinemia; one was borderline while two other relatives without the mutation had hyperapobetalipoproteinemia. Mutant low-density lipoprotein (LDL) was bound and degraded to a greater extent than normal LDL in cultured human fibroblasts. In conclusion, a new mutation, ApoB-100 Hopkins, was not linked to the hyperapobetalipoproteinemia phenotype, which also was segregating in this family. The increased affinity of this mutant LDL for the LDL receptor may be due to a specific effect of ApoB-100 Hopkins or to altered LDL size and composition.
Ladias JAA, Kwiterovich PO, Smith HH, Miller M, Bachorik PS, Forte T, Lusis AJ, Antonarakis SE. Apolipoprotein B-100 Hopkins (Arginine4019 [unk] Tryptophan)A New Apolipoprotein B-100 Variant in a Family With Premature Atherosclerosis and Hyperapobetalipoproteinemia. JAMA. 1989;262(14):1980–1988. doi:10.1001/jama.1989.03430140098032