Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein

CC Shoulders, DJ Brett, JD Bayllss… - Human molecular …, 1993 - academic.oup.com
CC Shoulders, DJ Brett, JD Bayllss, TME Narcisi, A Jarmuz, TT Grantham, PRD Leoni…
Human molecular genetics, 1993academic.oup.com
Abetallpoproteinemia is an inherited disorder of llpoprotein metabolism. Affected Individuals
produce virtually no circulating apollpoprotein B-containing llpoproteins (chylomicrons, very
low density llpoprotein, low intensity llpoprotein and llpoprotein (a)). Malabsorption of the
antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration.
Biochemical and genetic studies show that abetallpoproteinemia is not a defect of lipid
biosynthesis or of the apollpoprotein B gene. Instead a microsomal triglycerlde transfer …
Abstract
Abetallpoproteinemia is an inherited disorder of llpoprotein metabolism. Affected Individuals produce virtually no circulating apollpoprotein B-containing llpoproteins (chylomicrons, very low density llpoprotein, low intensity llpoprotein and llpoprotein (a)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration. Biochemical and genetic studies show that abetallpoproteinemia is not a defect of lipid biosynthesis or of the apollpoprotein B gene. Instead a microsomal triglycerlde transfer protein, which exists as a complex with protein disulphide Isomerase in the endoplasmic reticulum, has been Implicated. We have cloned and sequenced the human cDNA encoding microsomal triglyceride transfer protein. The predicted amino acid sequence shows extensive homology to vitellogenin, the precursor of the llpovitellin complex, which has been shown by X-ray crystallography to contain a large lipid storage cavity. Microsomal triglyceride transfer protein is expressed in ovary, testls and kidney, in addition to liver and small Intestine. A homozygous mutation that disrupts splicing has been identified in affected siblings with classical abetallpoproteinemia. These results elucidate a key process in the packaging of apollpoprotein B with lipid, and should increase our understanding of the processses regulating the production of atherogenic llpoproteins.
Oxford University Press