title: A truncated species of apolipoprotein B, B-83, associated with hypobetalipoproteinemia.
abstract: Familial hypobetalipoproteinemia, a syndrome associated with low plasma cholesterol levels, can be caused by apoB gene mutations. We identified a healthy 42-year-old man whose total plasma cholesterol level was 80 mg/dl. His plasma very low density lipoprotein (VLDL) contained a unique truncated apoB species, apoB-83, in addition to the normal B apolipoproteins, apoB-100 and apoB-48. Virtually no apoB-83 was detectable in his low density lipoprotein (LDL). From the subject's kindred, we identified nine other hypocholesterolemic subjects whose VLDL contained apoB-83. A tendency for cholelithiasis was noted in the apoB-83 heterozygotes, particularly in the older individuals. From the apparent size of apoB-83 on SDS-polyacrylamide gels and its reactivity with apoB-specific monoclonal antibodies, we estimated that it would contain approximately 3700-3800 amino acids. DNA sequencing of apoB genomic clones from two affected individuals revealed that apoB-83 was caused by a C----A transversion in exon 26 of the apoB gene (apoB cDNA nucleotide 11458). This mutation converts Ser-3750 (TCA) into a premature stop codon (TAA) and creates a unique MseI restriction endonuclease site. Thus, a single nucleotide transversion in the apoB gene results in a unique truncated apoB species, apoB-83, and the clinical syndrome of familial hypobetalipoproteinemia.
authors.affiliation: Gladstone Foundation Laboratories for Cardiovascular Research, University of California, San Francisco 94140-0608.
authors.forename: R V
authors.initials: RV
authors.lastname: Farese
authors.forename: A
authors.initials: A
authors.lastname: Garg
authors.forename: V R
authors.initials: VR
authors.lastname: Pierotti
authors.forename: G L
authors.initials: GL
authors.lastname: Vega
authors.forename: S G
authors.initials: SG
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D004247:DNA; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D001055:Apolipoproteins B; D004247:DNA