title: Truncated variants of apolipoprotein B cause hypobetalipoproteinaemia.
abstract: Familial hypobetalipoproteinaemia is a rare autosomal dominant disorder in which levels of apo-B-containing plasma lipoproteins are approximately half-normal in heterozygotes and virtually absent in homozygotes. Here we describe mutations of the apo-B gene that cause two different truncated variants of apo-B in unrelated individuals with hypobetalipoproteinaemia. One variant, apo-B(His1795----Met-Trp-Leu-Val-Thr-Term) is predicted to be 1799 amino acids long and arises from deletion of a single nucleotide (G) from leucine codon 1794. This protein was found at low levels in very low density and low density lipoprotein fractions in the blood. The second, shorter variant, apo-B(Arg1306----Term), is caused by mutation of a CpG dinucleotide in arginine codon 1306 converting it to a stop codon and predicting a protein of 1305 residues. The product of this allele could not be detected in the circulation. The differences in size and behaviour of these two variants compared to apo-B100 or apo-B48 point to domains that may be important for the assembly, secretion or stability of apo-B-containing lipoproteins.
authors.affiliation: Division of Molecular Medicine, MRC Clinical Research Centre, Harrow, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Collins
authors.forename: T J
authors.initials: TJ
authors.lastname: Knott
authors.forename: R J
authors.initials: RJ
authors.lastname: Pease
authors.forename: L M
authors.initials: LM
authors.lastname: Powell
authors.forename: S C
authors.initials: SC
authors.lastname: Wallis
authors.forename: S
authors.initials: S
authors.lastname: Robertson
authors.forename: C R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: R W
authors.initials: RW
authors.lastname: Milne
authors.forename: Y L
authors.initials: YL
authors.lastname: Marcel
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000097:blood / Q000235:genetics; D004262:DNA Restriction Enzymes; D005260:Female; D005784:Gene Amplification; D005796:Genes; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000235:genetics*; D007009:Hypolipoproteinemias / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol; D004262:DNA Restriction Enzymes