Document Detail

A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP).
MedLine Citation:
PMID:  21394827     Owner:  NLM     Status:  MEDLINE    
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 (PDI) and their localization at the endoplasmic reticulum. These children have a severe abetalipoproteinemia. Both of them had also a mild hypogammaglobulinemia. They are compound heterozygotes with c.619G>T and c.1237-28A>G mutations within the MTTP gene. mRNA analysis revealed abnormal splicing with deletion of exon 6 and 10, respectively. Deletion of exon 6 (Δ6-MTTP) introduced a frame shift in the reading frame and a premature stop codon at position 234. Despite the fact that Δ6-MTTP and Δ10-MTTP mutants were not capable of binding PDI, both MTTP mutant proteins normally localize at the endoplasmic reticulum. However, these two mutations induce a loss of MTTP triglyceride transfer activity. These two mutations lead to abnormal truncated MTTP proteins, incapable of binding PDI and responsible for the loss of function of MTTP, thereby explaining the severe abetalipoproteinemia phenotype of these children.
Véronique Pons; Corinne Rolland; Michel Nauze; Marie Danjoux; Gérald Gaibelet; Anne Durandy; Agnès Sassolas; Emile Lévy; François Tercé; Xavier Collet; Emmanuel Mas
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-14
Journal Detail:
Title:  Human mutation     Volume:  32     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-28     Completed Date:  2011-10-14     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  751-9     Citation Subset:  IM    
Copyright Information:
© 2011 Wiley-Liss, Inc.
INSERM/UMR 1048, Institut de Maladies Métaboliques et Cardiovasculaires, Université de Toulouse III, Toulouse, France.
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MeSH Terms
Abetalipoproteinemia / genetics*,  pathology*
Agammaglobulinemia / genetics
Alternative Splicing / genetics
Amino Acid Sequence
Carrier Proteins / genetics*,  metabolism
Endoplasmic Reticulum / metabolism
Exons / genetics*
Hela Cells
Hep G2 Cells
Microsomes / metabolism
Molecular Sequence Data
Mutation / genetics
Protein Binding / genetics
Protein Disulfide-Isomerases / genetics,  metabolism
Triglycerides / metabolism
Grant Support
MOP 10584//Canadian Institutes of Health Research
Reg. No./Substance:
0/Carrier Proteins; 0/Triglycerides; 0/microsomal triglyceride transfer protein; EC Disulfide-Isomerases
Erratum In:
Hum Mutat. 2011 Oct;32(10):1191-6

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