We report the characterization of a new truncated
apolipoprotein (
apo) B, originally identified in the plasma of a homozygous proband and three heterozygous family members with
hypobetalipoproteinemia. Using Western blotting, the truncated
apoB species was estimated to be 27.5% the size of
apoB-100. After fast
protein liquid chromatography of plasma from the proband (CD) and mother (OS), the truncated
apoB was eluted with particles whose sizes were between normal low and
high density lipoproteins. Sequencing of exons 21-24, including the intron-exon boundaries, revealed a T-->C transition at +2 of intron 24, homozygous in CD and heterozygous in OS, thus disrupting the 5' donor splice site and interrupting the translation of
serine. On the basis of this, the truncated
protein was estimated to be approximately
apoB-27.6. The reason for this approximation is that splice-junction mutations can generate different
mRNA transcripts, and the truncated
protein might represent a mixture of novel carboxy-terminal
peptides, terminated by in-frame
STOP codons. To date,
apoB-27.6 is the smallest truncated species identified in plasma and associated with
lipid. An explanation for this could be the hydrophobic nature of the novel carboxy-terminal
peptides, which might enable stabilization of the particles by solubilization of sufficient
lipid.