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Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia.

Authors: Narcisi, TM  Shoulders, CC  Chester, SA  Read, J  Brett, DJ  Harrison, GB  Grantham, TT  Fox, MF  Povey, S  De Bruin, TW 
Citation: Narcisi TM, etal., Am J Hum Genet. 1995 Dec;57(6):1298-310.
Pubmed: (View Article at PubMed) PMID:8533758

Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity.

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RGD Object Information
RGD ID: 1581045
Created: 2006-09-12
Species: All species
Last Modified: 2006-09-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.