Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B

Gastroenterology. 1996 Oct;111(4):1125-33. doi: 10.1016/s0016-5085(96)70082-3.


Fatty liver has been anecdotally associated with heterozygous hypobetalipoproteinemia. The aim of this study was to characterize the molecular defect in a subject with heterozygous hypobetalipoproteinemia (low-density lipoprotein cholesterol, 52 mg/dL; apolipoprotein [apo] B, 15 mg/dL) and otherwise unexplained fatty liver. Plasma lipoproteins were separated by ultracentrifugation, and apo B was analyzed by electrophoresis and immunoblotting. A fragment of genomic DNA corresponding to the 5' end of exon 26 of the apo B gene was amplified by polymerase chain reaction and sequenced. The plasma lipoproteins of the proband contained, besides normal apo B-100, a 200-kilodalton truncated apo B whose size suggested the presence of a mutation in exon 26 of the apo B gene. The nucleotide sequence of a fragment of the 5' end of exon 26 revealed that the proband was a heterozygote for a 14-nucleotide deletion, producing a frameshift resulting in a premature stop codon at residue 1768. This truncated apo B was named apo B-38.95. The proband's father was a carrier of the same mutation. Fatty liver in this subject with familial heterozygous hypobetalipoproteinemia most likely results from the inability of apo B-38.95 to export lipids from hepatocytes into the blood stream. Heterozygous hypobetalipoproteinemia should be considered in a hypolipidemic subject with an otherwise unexplained fatty liver.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins B / genetics*
  • Base Sequence
  • Exons
  • Fatty Liver / etiology*
  • Heterozygote
  • Humans
  • Hypobetalipoproteinemias / genetics*
  • Lipoproteins / blood
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational


  • Apolipoproteins B
  • Lipoproteins