Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia

Filippo, Mathilde Di; Crehalet, Hervé; Samson-Bouma, Marie Elisabeth; Bonnet, Véronique; Aggerbeck, Lawrence P.; Rabès, Jean-Pierre; Gottrand, Frédéric; Luc, Gérald; Bozon, Dominique; Sassolas, Agnès

doi:10.1194/jlr.m020024

Cited by 41 publications

(49 citation statements)

References 43 publications

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“…Discussion ABL is a rare autosomal recessive disorder caused by mutations in the MTP encoding gene [1,6,[8][9][10]13]. Many mutations were identified in the MTTP gene in patients with ABL [5]. Most of these are due to major truncations or large deletions [12].…”

Section: Casementioning

confidence: 99%

“…Loss of fat soluble vitamins due to fat malabsorption might lead to hepatic, neurologic and ophthalmologic symptoms in the form of spinocerebellar degeneration, coagulopathy and pigmented retinopathy [1,3,8,12]. Hepatic steatosis, fibrosis and cirrhosis were also reported in some cases [5].…”

Section: Introductionmentioning

confidence: 99%

“…Patients with ABL usually presented during infancy with history of failure to thrive, severe diarrhea and lipid malabsorption syndrome [2,5,8]. They exhibit symptoms of intestinal lipid malabsorption and low plasma lipid levels [1,5,6].…”

Section: Introductionmentioning

confidence: 99%

“…They exhibit symptoms of intestinal lipid malabsorption and low plasma lipid levels [1,5,6]. In later childhood, they present with ataxic neuropathy or retinopathy [2,8].…”

Section: Introductionmentioning

confidence: 99%

“…A beta lipoproteinemia (ABL; OMIM#200100) is a rare metabolic autosomal recessive disorder [1][2][3][4][5][6][7][8]. The prevalence is ranging between less than 1 in 100,000 [2,6] and less than 1 in one million [3].…”

Section: Introductionmentioning

confidence: 99%

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Abetalipoproteinemia: Three Case Reports, a Novel Microsomal Triglyceride Transfer Protein Gene Mutation and a Literature Review

Isa¹,

Mohamed²

2016

J Clin Case Rep

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Abetalipoproteinemia (ABL, OMIM 200100) is a very rare metabolic disease with reported prevalence of less than one case per 100,000. It is an autosomal recessive disease resulting from mutations in the gene encoding microsomal triglyceride transfer protein (MTP). Affected patients present with a wide range of clinical symptoms during infancy. Typical manifestations are failure to thrive, low level of cholesterol and fat malabsorption. Other features like fatty liver, acanthocytosis and anemia are usually present. Low fat diet and fat-soluble vitamins are the main stay of therapy. This is a retrospective review of three patients admitted to Salmaniya medical complex (SMC), Bahrain, with ABL. We presented the clinical presentations, diagnosis, response to medical therapy and outcome of these three infants along with a literature review about ABL. A novel MTP gene mutation, c.1508_1515delTGGCTACC (p.Leu503Hisfs*7, exon 11, MTTP), was detected. Two patients responded to dietary modifications and one deceased.

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Section: Casementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…They exhibit symptoms of intestinal lipid malabsorption and low plasma lipid levels [1,5,6]. In later childhood, they present with ataxic neuropathy or retinopathy [2,8].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Abetalipoproteinemia: Three Case Reports, a Novel Microsomal Triglyceride Transfer Protein Gene Mutation and a Literature Review

Isa¹,

Mohamed²

2016

J Clin Case Rep

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Molecular Genetics of Hypobetalipoproteinaemia and Abetalipoproteinaemia

Hooper

Burnett

2013

Encyclopedia of Life Sciences

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Genetic disorders of lipoprotein metabolism can cause marked hypocholesterolaemia with low or absent low‐density lipoprotein (LDL) cholesterol and apolipoprotein B (apoB) concentrations in plasma, depending on the gene involved and mode of inheritance of the condition, together with the severity of the mutation or mutations present. Hypobetalipoproteinaemia is defined as a plasma LDL cholesterol and apoB less than the 5th centile for age and sex, and when mutations in the APOB gene are inherited in a codominant fashion is known as familial hypobetalipoproteinaemia (FHBL). Abetalipoproteinaemia, which is clinically indistinguishable from homozygous FHBL, is a very rare recessive disorder caused by mutations in MTTP and characterised by the absence of apoB‐containing lipoproteins in the plasma. Loss‐of‐function mutations in PCSK9 , particularly nonsense mutations, are also associated with hypobetalipoproteinaemia, but lack any clinical features. More recently, mutations in ANGPTL3 were found to cause recessive familial combined hypolipidaemia, characterised by a reduction in all plasma lipids. Key Concepts: Hypobetalipoproteinaemia is defined as low levels (<5th centile) of plasma LDL cholesterol and apolipoprotein B, whereas in abetalipoproteinaemia these analytes may be undetectable. Heterozygous FHBL is generally caused by truncations in apoB, and is associated with hepatic steatosis and a low risk of cardiovascular disease. Homozygous FHBL and abetalipoproteinaemia result in a variable clinical phenotype and are caused by mutations in APOB and MTTP , respectively. Loss‐of‐function mutations in PCSK9 are associated with low plasma LDL cholesterol concentrations and low risk of cardiovascular disease, and no clinical phenotype. ANGPTL3 mutations cause familial combined hypolipidaemia, a newly described recessive condition characterised by reductions in all plasma lipids.

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As Little as Needed: The Extraordinary Case of a Mild Recessive Osteopetrosis Owing to a Novel Splicing Hypomorphic Mutation in the TCIRG1 Gene

Sobacchi

Pangrazio

Lopez

et al. 2014

Journal of Bone and Mineral Research

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Mutations in the TCIRG1 gene, coding for a subunit of the osteoclast proton pump, are responsible for more than 50% of cases of human malignant autosomal recessive osteopetrosis (ARO), a rare inherited bone disease with increased bone density owing to a failure in bone resorption. A wide variety of mutations has been described, including missense, nonsense, small deletions/insertions, splice-site mutations, and large genomic deletions, all leading to a similar severe presentation. So far, to the best of our knowledge, no report of a mild phenotype owing to recessive TCIRG1 mutations is present neither in our series of more than 100 TCIRG1-dependent ARO patients nor in the literature. Here we describe an 8-year-old patient referred to us with a clinical diagnosis of ARO, based on radiological findings; of note, no neurological or hematological defects were present in this girl. Surprisingly, we identified a novel nucleotide change in intron 15 of the TCIRG1 gene at the homozygous state, leading to the production of multiple aberrant transcripts, but also, more importantly, of a limited amount of the normal transcript. Our results show that a low level of normal TCIRG1 protein can dampen the clinical presentation of TCIRG1-dependent ARO. On this basis, a small amount of protein might be sufficient to rescue, at least partially, the severe ARO phenotype, and this is particularly important when gene therapy approaches are considered. In addition, we would also recommend that the TCIRG1 gene be included in the molecular diagnosis of mild forms of human ARO. © 2014 Italian National Research Council. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia

Cited by 41 publications

References 43 publications

Abetalipoproteinemia: Three Case Reports, a Novel Microsomal Triglyceride Transfer Protein Gene Mutation and a Literature Review

Abetalipoproteinemia: Three Case Reports, a Novel Microsomal Triglyceride Transfer Protein Gene Mutation and a Literature Review

Molecular Genetics of Hypobetalipoproteinaemia and Abetalipoproteinaemia

As Little as Needed: The Extraordinary Case of a Mild Recessive Osteopetrosis Owing to a Novel Splicing Hypomorphic Mutation in the TCIRG1 Gene

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