title: Familial hypobetalipoproteinemia due to a novel early stop mutation.
abstract: 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.
authors.affiliation: Cardiovascular Research Group, Division of Cardiovascular and Endocrine Science, Core Technology Facility, 3rd Floor, University of Manchester, 46 Garfton Street, Manchester M13 9NT, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durrington
authors.forename: Valentine
authors.initials: V
authors.lastname: Charlton-Menys
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Packard
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatnagar
authors.forename: John
authors.initials: J
authors.lastname: Scott
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele