title: Two distinct truncated apolipoprotein B species in a kindred with hypobetalipoproteinemia.
abstract: Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parental alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited greater than 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Atherosclerosis and Lipid Research Washington University School of Medicine, St. Louis, Missouri.
authors.forename: E S
authors.initials: ES
authors.lastname: Krul
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: P
authors.initials: P
authors.lastname: Talmud
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: S
authors.initials: S
authors.lastname: Turner
authors.forename: A C
authors.initials: AC
authors.lastname: Goldberg
authors.forename: K
authors.initials: K
authors.lastname: Cook
authors.forename: E
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: G
authors.initials: G
authors.lastname: Schonfeld
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001055:Apolipoproteins B / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics*; D007009:Hypolipoproteinemias / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D013917:Thrombin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D002784:Cholesterol; D013917:Thrombin