A Novel Nontruncating APOB Gene Mutation, R463W, Causes Familial Hypobetalipoproteinemia*

Familial hypobetalipoproteinemia (FHBL), an auto-somal co-dominant disorder, is associated with re-duced plasma concentrations (<5th percentile for age and sex) of apolipoprotein (apo) B and -migrating lipoproteins. To date, only mutations in APOB encod-ing prematurely truncated apoB have been found in FHBL. We discovered a novel APOB gene mutation, namely R463W, in an extended Christian Lebanese FHBL kindred. Heterozygotes for R463W had the typ-ical FHBL phenotype, whereas homozygotes had barely detectable apoB-100. The effect of the R463W mutation on apoB secretion was examined using trans-fected McA-RH7777 cells that expressed one of two recombinant human apoBs, namely B48 and B17. In both cases, the mutant proteins (B48RW and B17RW