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

  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},
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… 
Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia[S]
This investigation provides an example of a functional analysis of unclassified variations, which is an absolute necessity for the molecular diagnosis of atypical ABL cases.
Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene
A novel mutation in MTTP gene is discovered and the diagnosis of abetalipoproteinemia is confirmed in new Tunisian families with severe deficiency of plasma low-density lipoprotein (LDL) and apo B.
A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases.
The first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12, a six-year-old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels.
Congenital Disorders of Lipid Transport
  • N. Davidson, E. Levy
  • Biology
    Textbook of Pediatric Gastroenterology, Hepatology and Nutrition
  • 2021
Recognition and understanding of the underlying mechanisms of altered lipid transport in the background of mutations of these genes have led to the implementation of preventive strategies to attenuate the development of fat-soluble vitamin deficiencies, particularly vitamin A, D, E, and K.
Current Diagnosis and Management of Abetalipoproteinemia
Diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease are proposed and low-density lipoprotein cholesterol (LDL-C) and apoB) can be useful in universal or opportunistic screening for the disease.


Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia
It is suggested that genetic and non‐genetic factors can modulate the clinical impact of mutant MTP in ABL patients.
Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.
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.
Identification of patients with abetalipoproteinemia and homozygous familial hypobetalipoproteinemia in Tunisia.
Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia.
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.
A Novel Abetalipoproteinemia Genotype
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.
Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia
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.
Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein.
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.
Abetalipoproteinemia caused by maternal isodisomy of chromosome 4q containing an intron 9 splice acceptor mutation in the microsomal triglyceride transfer protein gene.
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.
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.