K. Ohashi et al., A TRUNCATED SPECIES OF APOLIPOPROTEIN-B (B-38.7) IN A PATIENT WITH HOMOZYGOUS HYPOBETALIPOPROTEINEMIA ASSOCIATED WITH DIABETES-MELLITUS, Arteriosclerosis, thrombosis, and vascular biology, 18(8), 1998, pp. 1330-1334
Familial hypobetalipoproteinemia is caused by mutations in the apolipo
protein (apo) B gene. We identified a 57-year-old woman whose plasma t
otal cholesterol and apoB levels were 2.17 mmol/L and 0.03 g/L, respec
tively. Separation of plasma lipoproteins by sodium dodecyl sulfate-po
lyacrylamide gel electrophoresis revealed the absence of apoB-100 and
the presence of a faster-migrating form of apoB with an apparent M-r o
f 195 kDa. Direct sequencing of a polymerase chain reaction-amplified
fragment of the patient's apoB gene DNA revealed a single C-->T transi
tion at nucleotide 5472 that converts glutamine 1755 (CAA) to a stop c
odon (TAA). We predict this novel nonsense mutation of the apoB gene t
o produce a truncated protein that contains 1754 amino-terminal amino
acid residues of apoB-100. We designated this mutant form of apoB apoB
-38.7 by following the centile nomenclature of the apoB species. The s
ame mutation was found in both of her children. The proband revealed c
linical findings of retinitis pigmentosa, acanthocytosis, and loss of
deep tendon reflexes that are characteristic of severe hypobetalipopro
teinemia. In addition, the proband had type II diabetes mellitus with
nephropathy, anemia, cholelithiasis, hepatic hemangioma, bronchiectasi
s, and extensive calcification of major arteries including, the celiac
, splenic, and renal. In summary, we have found a novel truncated apoB
, apoB-38.7, in a patient with an unusual presentation of hypobetalipo
proteinemia that includes diabetes mellitus and extensive arterial cal
cification.