title: Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Modena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tarugi
authors.forename: A
authors.initials: A
authors.lastname: Lonardo
authors.forename: G
authors.initials: G
authors.lastname: Ballarini
authors.forename: A
authors.initials: A
authors.lastname: Grisendi
authors.forename: M
authors.initials: M
authors.lastname: Pulvirenti
authors.forename: A
authors.initials: A
authors.lastname: Bagni
authors.forename: S
authors.initials: S
authors.lastname: Calandra
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D005091:Exons; D005234:Fatty Liver / Q000209:etiology*; D006579:Heterozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D001055:Apolipoproteins B; D008074:Lipoproteins