FATTY LIVER IN HETEROZYGOUS HYPOBETALIPOPROTEINEMIA CAUSED BY A NOVELTRUNCATED FORM OF APOLIPOPROTEIN-B

Fatty liver has been anecdotally associated with heterozygous hypobeta lipoproteinemia. The aim of this study was to characterize the molecul ar 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 electroph oresis and immunoblotting. A fragment of genomic DNA corresponding to the 5' end of exon 26 of the apo B gene was amplified by polymerase ch ain reaction and sequenced. The plasma lipoproteins of the proband con tained, besides normal apo B-100, a 200-kilodalton truncated apo B who se size suggested the presence of a mutation in exon 26 of the apo B g ene. The nucleotide sequence of a fragment of the 5' end of exon 26 re vealed that the proband was a heterozygote for a 14-nucleotide deletio n, producing a frameshift resulting in a premature stop codon at resid ue 1768. This truncated apo B was named apo B-38.95. The proband's fat her was a carrier of the same mutation. Fatty liver in this subject wi th familiar heterozygous hypobetalipoproteinemia most likely results f rom the inability of apo B-38.95 to export lipids from hepatocytes int o the blood stream. Heterozygous hypobetalipoproteinemia should be con sidered in a hypolipidemic subject with an otherwise unexplained fatty liver.