Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene.
We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and 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 premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous 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 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.
Tarugi
P
P
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via Campi 287, I-41100 Modena, Italy. tarugi@unimo.it
Lonardo
A
A
Gabelli
C
C
Sala
F
F
Ballarini
G
G
Cortella
I
I
Previato
L
L
Bertolini
S
S
Cordera
R
R
Calandra
S
S
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D002499:Centrifugation, Density Gradient; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013631:Tangier Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins