Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.

A kindred with apolipoprotein E deficiency and a truncated lower molecular weight apoE mutant, designated apoE-3Washington, has been identified. Gel electrophoresis demonstrated complete absence of the normal apoE isoproteins and the presence of a small quantity of a lower molecular weight apoE. Pla...

Full description

Bibliographic Details
Main Authors: P Lohse, HB Brewer, 3rd, MS Meng, SI Skarlatos, JC LaRosa, HB Brewer, Jr
Format: Article
Language:English
Published: Elsevier 1992-11-01
Series:Journal of Lipid Research
Online Access:http://www.sciencedirect.com/science/article/pii/S002222752041380X
id doaj-8c6e8db4959a4e1694f1929a794360bf
record_format Article
spelling doaj-8c6e8db4959a4e1694f1929a794360bf2021-04-26T05:52:21ZengElsevierJournal of Lipid Research0022-22751992-11-01331115831590Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.P Lohse0HB Brewer, 3rd1MS Meng2SI Skarlatos3JC LaRosa4HB Brewer, Jr5Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.A kindred with apolipoprotein E deficiency and a truncated lower molecular weight apoE mutant, designated apoE-3Washington, has been identified. Gel electrophoresis demonstrated complete absence of the normal apoE isoproteins and the presence of a small quantity of a lower molecular weight apoE. Plasma apoE levels in the proband were approximately 4% of normal. This marked deficiency of apoE resulted in delayed uptake of chylomicron and very low density lipoprotein (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild hypertriglyceridemia, and the development of type III hyperlipoproteinemia. Sequence analysis of the patient's apoE gene revealed a single nucleotide substitution of an A for a G, which converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus leading to the synthesis of a truncated E apolipoprotein of 209 amino acids with a molecular mass of 23.88 kDa. Northern blot analysis of differentiated monocyte-derived macrophages demonstrated a mutant mRNA indistinguishable in size from normal apoE mRNA. The nucleotide substitution also resulted in the formation of a new restriction site for Mae I. Using this enzyme we were able to establish that the proband is a homozygote and that her two offsprings are heterozygous for the epsilon-3Washington allele. These data demonstrate that the striking deficiency of apoE-3Washington results in a moderate form of type III hyperlipoproteinemia. The clinical presentation also suggests a dispensable role of apoE in the nervous system and in immunoregulation.http://www.sciencedirect.com/science/article/pii/S002222752041380X
collection DOAJ
language English
format Article
sources DOAJ
author P Lohse
HB Brewer, 3rd
MS Meng
SI Skarlatos
JC LaRosa
HB Brewer, Jr
spellingShingle P Lohse
HB Brewer, 3rd
MS Meng
SI Skarlatos
JC LaRosa
HB Brewer, Jr
Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
Journal of Lipid Research
author_facet P Lohse
HB Brewer, 3rd
MS Meng
SI Skarlatos
JC LaRosa
HB Brewer, Jr
author_sort P Lohse
title Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
title_short Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
title_full Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
title_fullStr Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
title_full_unstemmed Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
title_sort familial apolipoprotein e deficiency and type iii hyperlipoproteinemia due to a premature stop codon in the apolipoprotein e gene.
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 1992-11-01
description A kindred with apolipoprotein E deficiency and a truncated lower molecular weight apoE mutant, designated apoE-3Washington, has been identified. Gel electrophoresis demonstrated complete absence of the normal apoE isoproteins and the presence of a small quantity of a lower molecular weight apoE. Plasma apoE levels in the proband were approximately 4% of normal. This marked deficiency of apoE resulted in delayed uptake of chylomicron and very low density lipoprotein (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild hypertriglyceridemia, and the development of type III hyperlipoproteinemia. Sequence analysis of the patient's apoE gene revealed a single nucleotide substitution of an A for a G, which converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus leading to the synthesis of a truncated E apolipoprotein of 209 amino acids with a molecular mass of 23.88 kDa. Northern blot analysis of differentiated monocyte-derived macrophages demonstrated a mutant mRNA indistinguishable in size from normal apoE mRNA. The nucleotide substitution also resulted in the formation of a new restriction site for Mae I. Using this enzyme we were able to establish that the proband is a homozygote and that her two offsprings are heterozygous for the epsilon-3Washington allele. These data demonstrate that the striking deficiency of apoE-3Washington results in a moderate form of type III hyperlipoproteinemia. The clinical presentation also suggests a dispensable role of apoE in the nervous system and in immunoregulation.
url http://www.sciencedirect.com/science/article/pii/S002222752041380X
work_keys_str_mv AT plohse familialapolipoproteinedeficiencyandtypeiiihyperlipoproteinemiaduetoaprematurestopcodonintheapolipoproteinegene
AT hbbrewer3rd familialapolipoproteinedeficiencyandtypeiiihyperlipoproteinemiaduetoaprematurestopcodonintheapolipoproteinegene
AT msmeng familialapolipoproteinedeficiencyandtypeiiihyperlipoproteinemiaduetoaprematurestopcodonintheapolipoproteinegene
AT siskarlatos familialapolipoproteinedeficiencyandtypeiiihyperlipoproteinemiaduetoaprematurestopcodonintheapolipoproteinegene
AT jclarosa familialapolipoproteinedeficiencyandtypeiiihyperlipoproteinemiaduetoaprematurestopcodonintheapolipoproteinegene
AT hbbrewerjr familialapolipoproteinedeficiencyandtypeiiihyperlipoproteinemiaduetoaprematurestopcodonintheapolipoproteinegene
_version_ 1721508191094702080