Apolipoprotein CIISt. Michael. Familial apolipoprotein CII deficiency associated with premature vascular disease

A 60-yr-old woman and her brother, products of a consanquinous mating, were chylomicronemic. The chylomicronemia in both subjects was found to be due to the absence of functional apoCII. A mutant form, designated apoCIISt. Michael (apoCIIs), was identified by two-dimensional electrophoresis and Western blot using anti-apoCII antiserum. The isoelectric point of apoCIIs was similar to that of normal apoCII, but its apparent molecular weight was 3,000 greater. Tryptic peptides of apoCIIs were identified that had retention times in reverse-phase high pressure liquid chromatography and amino acid compositions indistinguishable from that of residues 1 to 48 and 51 to 55 of normal apoCII. The complete sequence of apoCIIs was deduced from a combination of the sequence analysis of tryptic peptides corresponding to residues 56 through 96 and the known sequence of the apoCII gene. ApoCIIs differed from apoCII at residue 70 where Gln70 was replaced by Pro70 and the sequence terminated with Pro96. This is consistent with a base insertion in the codon for Asp69 or Gln70 in the apoCII gene and a subsequent translation reading frame shift. Both patients were homozygous for apoE-4. This and the absence of normal apoCII is consistent with homozygozity at the apoE-CII gene locus on chromosome 19. Both siblings and several relatives had premature ischemic vascular disease, in contrast with its apparent absence in other apoCII-deficient families.