Four Novel Mutations in APOB Causing Heterozygous and Homozygous Familial Hypobetalipoproteinemia

A.J. Whitfield, A.D. Marais, K. Robertson, Hugh Barrett, Frank Van Bockxmeer, John Burnett

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    24 Citations (Scopus)


    Familial hypobetalipoproteinemia (FHBL) is a rare codominant disorder of lipoprotein metabolism characterized by low levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. Heterozygotes for FHBL have less-than-half normal LDL-cholesterol and apoB concentrations, whereas homozygotes have extremely low or undetectable LDL-cholesterol and apoB levels. These reductions in LDL-cholesterol and apoB have been suggested to provide FHBL subjects with resistance to atherosclerosis. FHBL can be caused by mutations in the APOB gene on chromosome 2. We present four novel mutations and one previously described mutation in APOB causing FHBL in five families. Immunoblotting and DNA sequencing were used to characterize the novel mutation apoB-40.3 (c.5564underscore;5565insC) and the previously reported mutation apoB-80.5 (c.11040T>G). The apoB-6.9 (c.1018underscore;1025del) and apoB-25.8 (c.3600T>A) mutations were identified by DNA sequence analysis, as variants shorter than apoB-31 are not detectable in plasma. A fifth mutation, the splice variant c.82+1G>A, was identified by sequencing and was found in a homozygous subject. In ∼50% of the FHBL subjects, plasma alanine aminotransferase concentrations were mildly increased, suggestive of fatty liver. All affected FHBL subjects had low to low-normal serum vitamin E concentrations, highlighting the important and recognized relationship between lipid and vitamin E concentrations. © 2003 Wiley-Liss, Inc.
    Original languageEnglish
    Pages (from-to)178-183
    JournalHuman Mutation
    Issue number2
    Publication statusPublished - 2003


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