Vol. 154, No. 1, 1988 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS July 15, 1988 Pages 73-79 APOLIPOPROTEIN C-II DEFICIENCY: IDENTIFICATION OF A STRUCTURAL VARIANT ApoC-IIPADOVA Silvia S. Fojo, Giovgnella Baggio*, Carlo Gabelli*, Kayoko Higuchi, Marina Bojanovski , Richard E. Gregg and H. Bryan Brewer, Jr. Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 + * University of Padova, Padova, Italy Medizinische Hochschule Hannover, Hannover, West Germany Received April 25, 1988 SUMMARY: Apolipoprotein(apo) C-II DNA, RNA and protein from a patient with a familial deficiency of apoC-II were evaluated and compared to normal individuals. No major defect of the apoC-II gene could be detected by Southern blot hybridiza- tion. Northern and slot blot analyses of total liver RNA documented normal levels of a normal sized apoC-II mRNA. Immunohistochemical studies of the liver of the apoC-II deficient patient revealed a normal to slightly elevated intracellular content of the C-II apolipoprotein. Plasma apoC-II was 3 to 5% of normal apoC-II levels and exhibited abnormal electrophoretic mobility on two dimensional gel electrophoresis and immunoblotting. We postulate that at the molecular level, the deficiency of apoC-II in the plasma of this patient results from a structural defect in the coding portion of the apoC-II gene leading to either defective secretion of cellular apoC-II or increased catabolism of a structurally defective apoC-II in plasma. Familial deficiency of apoC-II is a rare disease inherited as an autosomal recessive trait. Patients homozygous for the disease may present with lipemia retinales, eruptive xanthomas, and pancreatitis (l-7). The syndrome is also characterized by elevated fasting triglycerides and chylomicrons, decreased LDL and HDL concentrations, and a type I lipoprotein phenotype. The diagnosis of apoC-II deficiency is confirmed by finding reduced or absent levels of apoC-II and the absence of post-heparin plasma lipoprotein lipase activity which may be corrected by the addition of normal apoC-II containing plasma. Patients with near normal levels of a nonfunctional apoC-II varient are given the same diagnosis. Infusions of normal plasma (1,3,7), isolated apoC-II fractions (5), or synthetic apoC-II fragments (7) result in transient normalization of plasma triglycerides and lipoproteins in these patients. The marked aberration of triglyceride metabolism evident in patients with a deficiency of apoC-II has served to underscore the importance of apoC-II as the physiological activator of lipoprotein lipase. Of the various families with a defect in apoC-II that have been described, an abnormal plasma apoC-II variant has been isolated and the protein defect 0006-291X/88 $1.50 73