title: Variable phenotypic expression of homozygous familial hypobetalipoproteinaemia due to novel APOB gene mutations.
abstract: Homozygous familial hypobetalipoproteinaemia (Ho-FHBL) is a rare co-dominant disorder characterized by extremely low levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Most patients with Ho-FHBL have mutations in APOB gene resulting in truncated apoBs. Some patients are asymptomatic, while others have fatty liver, intestinal fat malabsorption and neurological dysfunctions. We investigated three adult subjects with severe hypobetalipoproteinaemia and a family history of FHBL. Proband FHBL-47 had liver cirrhosis with hepatocarcinoma and a renal carcinoma but no clinical manifestations related to FHBL. He was a compound heterozygote for a 7-bp deletion in exon 21 and a base insertion in exon 26 resulting in truncated apoBs (apoB-22.46/apoB-66.51). Proband FHBL-53, with severe hepatic steatosis and fibrosis, had a nonsense mutation in exon 19 resulting in a truncated apoB (apoB-20.61) and a rare nucleotide substitution in intron 14 (c.2068-4T>A). The latter was also present in her daughter, found to have low plasma LDL-C and apoB. Proband FHBL-82 had chronic diarrhoea and steatorrhoea. She was found to be homozygous for a nonsense mutation in exon 24 resulting in a truncated apoB (apoB-26.65). In adult subjects, the presence of chronic liver disease and chronic diarrhoea, when associated with severe hypobetalipoproteinaemia, may lead to the diagnosis of Ho-FHBL.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Di Leo
authors.forename: L
authors.initials: L
authors.lastname: Magnolo
authors.forename: M
authors.initials: M
authors.lastname: Bertolotti
authors.forename: M
authors.initials: M
authors.lastname: Bourbon
authors.forename: S
authors.initials: S
authors.lastname: Carmo Pereira
authors.forename: M
authors.initials: M
authors.lastname: Pirisi
authors.forename: S
authors.initials: S
authors.lastname: Calandra
authors.forename: P
authors.initials: P
authors.lastname: Tarugi
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: D001055:Apolipoproteins B