Dysbetalipoproteinemia in a Kindred With Hypobetalipoproteinemia Due to Mutations in the Genes for ApoB (ApoB-70.5)

Abstract We identified the first insertion mutation that specifies an apolipoprotein (apo)B truncation, apoB-70.5, in a father and son with hypobetalipoproteinemia (total and low-density lipoprotein [LDL] cholesterol <5th percentile, plasma apoB levels approximately one third of normal). The mutation is due to insertion of an adenine (A) into a 7-A repeat between cDNA position 9754 and 9760 of the apoB gene, resulting in a frame shift of 13 new amino acids and a termination codon at amino acid residue 3197. The DNA mutation cosegregated with the apoB truncation and hypobetalipoproteinemia in the kindred. The two apoB-70_5/apoB-100 heterozygotes also are apoE2 homozygotes by genotyping; /3-very-low-density lipo-protein (VLDL) was present, and VLDL cholesterol/trigh/c-eride ratios were increased (0.29) in the plasmas of both. Density gradient ultracentrifugation and gel filtration chroma