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

We report the clinical phenotype in three kindreds with familial heterozygo us hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein B s (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three car-tiers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea a nd 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 prematu re cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygo us 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 carrie r, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apo Bs (< apoB-48), but its occurrence needs additional environmental factors i n carriers of longer apoB forms; ii) intestinal lipid malabsorption develop s only in carriers of short truncated apoBs, which are not secreted into th e plasma; and ih) cerebrovascular disease due to premature atherosclerosis may occur even in FHRL subjects.