Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene

Patrizia Tarugi, Amedeo Lonardo, Carlo Gabelli, Franca Sala, Giorgia Ballarini, Irene Cortella, Lorenzo Previato, Stefano Bertolini, Renzo Cordera, Sebastiano Calandra

Research output: Contribution to journalArticlepeer-review

Abstract

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (<apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.

Original languageEnglish
Pages (from-to)1552-1561
Number of pages10
JournalJournal of Lipid Research
Volume42
Issue number10
Publication statusPublished - 2001

Keywords

  • Carotid atherosclerosis
  • Fatty liver
  • Lipid malabsorption
  • Truncated apoBs

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene'. Together they form a unique fingerprint.

Cite this