A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP)

@article{Pons2011ASF,
  title={A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP)},
  author={V{\'e}ronique Pons and Corinne Rolland and Michel Nauze and Marie Danjoux and Gérald Gaibelet and Anne Durandy and Agn{\`e}s Sassolas and Emile Levy and François Tercé and Xavier Collet and Emmanuel Mas},
  journal={Human Mutation},
  year={2011},
  volume={32}
}
Abetalipoproteinemia is a rare autosomal recessive disease characterized by low lipid levels and by the absence of apoB‐containing lipoproteins. It is the consequence of microsomal triglyceride transfer protein (MTTP) deficiency. We report two patients with new MTTP mutations. We studied their functional consequences on the triglyceride transfer function using duodenal biopsies. We transfected MTTP mutants in HepG2 and HeLa cells to investigate their association with protein disulfide isomerase… 
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TLDR
It is suggested that genetic and non‐genetic factors can modulate the clinical impact of mutant MTP in ABL patients.
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TLDR
Results indicated that defects of the MTP gene are the proximal cause of ABL, with a patient having the Asn780Tyr mutation having none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable.
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TLDR
It is established 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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TLDR
Results indicate that a positively charged amino acid at position 540 in the 97-kDa subunit is critical for the productive association with protein disulfide isomerase.
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TLDR
The results indicate that a defect in the gene for the large subunit of MTP is the proximal cause of abetalipopro-teinaemia in these two subjects, and that MTP are required for the secretion of plasma lipoproteins that contain apolipoprotein B.
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TLDR
Cloned and sequenced the human cDNA encoding microsomal triglyceride transfer protein, which exists as a complex with protein disulphide isomerase in the endoplasmic reticulum, and elucidate a key process in the packaging of apolipoprotein B with lipid.
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TLDR
A patient with ABL is described, inherited as a homozygous intron 9 splice acceptor G(-1)-to-A mutation of the transfer protein gene, resulting in a 36 amino acids, in-frame deletion of sequence encoded by exon 10.
Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function.
TLDR
It is shown that ABL is characterized by immune defects affecting presentation of self and microbial lipid antigens by group 1 (CD1a, CD1b,CD1c) and group 2 ( CD1d) CD1 molecules, which highlights MTP as a unique regulator of human metabolic and immune pathways.
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