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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Novel mutations in SAR1B and MTTP genes in Tunisian children with chylomicron retention disease and abetalipoproteinemia
Gene, Volume 512, No. 1, Year 2013
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Description
Monogenic hypobetalipoproteinemias include three disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) with recessive transmission and familial hypobetalipoproteinemia (FHBL) with dominant transmission. We investigated three unrelated Tunisian children born from consanguineous marriages, presenting hypobetalipoproteinemia associated with chronic diarrhea and retarded growth. Proband HBL-108 had a moderate hypobetalipoproteinemia, apparently transmitted as dominant trait, suggesting the diagnosis of FHBL. However, she had no mutations in FHBL candidate genes (APOB, PCSK9 and ANGPTL3). The analysis of MTTP gene was also negative, whereas SAR1B gene resequencing showed that the patient was homozygous for a novel mutation (c.184G>A), resulting in an amino acid substitution (p.Glu62Lys), located in a conserved region of Sar1b protein. In the HBL-103 and HBL-148 probands, the severity of hypobetalipoproteinemia and its recessive transmission suggested the diagnosis of ABL. The MTTP gene resequencing showed that probands HBL-103 and HBL-148 were homozygous for a nucleotide substitution in the donor splice site of intron 9 (c.1236+2T>G) and intron 16 (c.2342+1G>A) respectively. Both mutations were predicted in silico to abolish the function of the splice site. In vitro functional assay with splicing mutation reporter MTTP minigenes showed that the intron 9 mutation caused the skipping of exon 9, while the intron 16 mutation caused a partial retention of this intron in the mature mRNA. The predicted translation products of these mRNAs are non-functional truncated proteins. The diagnosis of ABL and CMRD should be considered in children born from consanguineous parents, presenting chronic diarrhea associated with hypobetalipoproteinemia. © 2012 Elsevier B.V.
Authors & Co-Authors
Magnolo, Lucia
Italy, Modena
Università Degli Studi Di Modena e Reggio Emilia
Najah, Mohamed
Tunisia, Monastir
Université de Monastir
Fancello, Tatiana
Italy, Modena
Università Degli Studi Di Modena e Reggio Emilia
Di Leo, Enza
Italy, Modena
Università Degli Studi Di Modena e Reggio Emilia
Pinotti, Elisa
Italy, Modena
Università Degli Studi Di Modena e Reggio Emilia
Brini, InèS Zerzeri
Tunisia, Tunis
Université de Tunis el Manar, Hôpital D'enfants Béchir Hamza de Tunis
Gueddiche, Néji M.
Tunisia, Monastir
Chu Fattouma-bourguiba
Calandra, Sebastiano
Italy, Modena
Università Degli Studi Di Modena e Reggio Emilia
Slimene, Naceur M.
Tunisia, Monastir
Université de Monastir
Tarugi, Patrizia
Italy, Modena
Università Degli Studi Di Modena e Reggio Emilia
Statistics
Citations: 31
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1016/j.gene.2012.09.117
ISSN:
03781119
e-ISSN:
18790038
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health