Familial hypobetalipoproteinemia due to a novel early stop mutation

Paul N. Durrington, Valentine Charlton-Menys, Christopher J. Packard, Muriel J. Caslake, Jian Wang, Deepak Bhatnagar, John Scott, Robert A. Hegele

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    Background: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder associated with low circulating levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (ApoB). A proband was identified in whom the condition was due to an E110X mutation of APOB, creating a particularly early truncation of ApoB in the region of the molecule necessary for very-low-density lipoprotein (VLDL) assembly. The mutation was also associated with nonalcoholic fatty liver disease. Objective: To assess the effect of the mutation on metabolism and the formation of VLDL and LDL subfractions. Results: Both the proband and his son, who had the same mutation, had low LDL cholesterol and decreased ApoB, but an increased small-dense LDL level. Lipoprotein profiles were normal in the proband's sister and grandson, in whom the mutation was absent. In the proband. there was a profoundly diminished rate of production of VLDL-2. VLDL-1 production, however, was relatively preserved and, because of its decreased catabolism, its pool size was increased. Direct formation of intermediate-density lipoprotein (IDL) and LDL was undetectable. Intermediate-density lipoprotein catabolism was greatly increased and its conversion to LDL was increased. The LDL produced was entirely small-dense LDL. High-density lipoprotein cholesterol levels were low, perhaps also related to the relative increase in VLDL-1, which is an avid acceptor of cholesteryl ester. Conclusions: This novel mutation provides evidence to support the hypothesis that hepatic production of large VLDL-1 leads to the creation of small-dense LDL. © 2008 National Lipid Association.
    Original languageEnglish
    Pages (from-to)384-390
    Number of pages6
    JournalJournal of Clinical Lipidology
    Issue number5
    Publication statusPublished - Oct 2008


    • Apolipoprotein B gene
    • Familial hypobetalipoproteinemia
    • HDL composition
    • Small-dense LDL


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