Apolipoprotein B-100 has a crucial structural role in the formation of VLDL and
LDL.
Familial hypobetalipoproteinemia, a syndrome in which the concentration of
LDL cholesterol in plasma is abnormally low, can be caused by mutations in the
apo B gene that prevent the translation of a full-length
apo B-100 molecule. Prior studies have revealed that truncated species of
apo B [e.g.,
apo B-37 (1728
amino acids),
apo B-46 (2057
amino acids)] can occasionally be identified in the plasma of subjects with
familial hypobetalipoproteinemia; in each of these cases, the truncated
apo B species has been a prominent
protein component of VLDL. In this report, we describe a kindred with
hypobetalipoproteinemia in which the plasma of four affected heterozygotes contained a unique truncated
apo B species, apo
B-31.
Apolipoprotein B-31 is caused by the deletion of a single
nucleotide in the
apo B gene, and it is predicted to contain 1425
amino acids.
Apolipoprotein B-31 is the shortest of the mutant
apo B species to be identified in the plasma of a subject with
hypobetalipoproteinemia. In contrast to longer truncated
apo B species, apo
B-31 was undetectable in the VLDL and the
LDL; however, it was present in the HDL fraction and the
lipoprotein-deficient fraction of plasma. The density distribution of apo
B-31 in the plasma suggests the possibility that the amino-terminal 1425
amino acids of
apo B-100 are sufficient to permit the formation and secretion of small, dense
lipoproteins but are inadequate to support the formation of the more
lipid-rich VLDL and
LDL particles.