title: Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene.
abstract: BACKGROUND
  Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder of lipid metabolism characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal triglyceride transfer protein (MTP; OMIM 157147). In the present study we investigated two unrelated Tunisian patients, born from consanguineous marriages, with severe deficiency of plasma low-density lipoprotein (LDL) and apo B.
  
  
  METHODS
  Intestinal biopsies were performed and The MTTP gene was amplified by Polymerase chain reaction then directly sequenced in patients presenting chronic diarrhea and retarded growth.
  
  
  RESULTS
  First proband was homozygous for a novel nucleotide deletion (c. 2611delC) involving the exon 18 of MTTP gene predicted to cause a non functional protein of 898 amino acids (p.H871I fsX29). Second proband was homozygous for a nonsense mutation in exon 8 (c.923 G > A) predicted to cause a truncated protein of 307 amino acids (p.W308X), previously reported in ABL patients.
  
  
  CONCLUSIONS
  We discovered a novel mutation in MTTP gene and we confirmed the diagnosis of abetalipoproteinemia in new Tunisian families.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8134027928652779.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Najah
authors.forename: Sarraj Mohamed
authors.initials: SM
authors.lastname: Youssef
authors.forename: Hrira Mohamed
authors.initials: HM
authors.lastname: Yahia
authors.forename: Slimani
authors.initials: S
authors.lastname: Afef
authors.forename: Jelassi
authors.initials: J
authors.lastname: Awatef
authors.forename: Hammami
authors.initials: H
authors.lastname: Saber
authors.forename: Najjar Mohamed
authors.initials: NM
authors.lastname: Fadhel
authors.forename: Agnès
authors.initials: A
authors.lastname: Sassolas
authors.forename: Slimane Mohamed
authors.initials: SM
authors.lastname: Naceur
mesh_terms: D000012:Abetalipoproteinemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood / Q000172:deficiency; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics*; D002908:Chronic Disease; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003967:Diarrhea / Q000235:genetics; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics; D040941:Heredity; D006720:Homozygote; D006801:Humans; D007223:Infant; D008077:Lipoproteins, LDL / Q000097:blood / Q000172:deficiency; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D012720:Severity of Illness Index; D014416:Tunisia; D055815:Young Adult
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D002352:Carrier Proteins; D018389:Codon, Nonsense; D008077:Lipoproteins, LDL; C106092:microsomal triglyceride transfer protein
references.citation: Hum Mutat. 2000 Mar;15(3):294-5
references.pmid: 10679949
references.citation: Orphanet J Rare Dis. 2010 Sep 29;5:24
references.pmid: 20920215
references.citation: J Lipid Res. 2003 Jan;44(1):22-32
references.pmid: 12518019
references.citation: J Lipid Res. 2000 Aug;41(8):1199-204
references.pmid: 10946006
references.citation: Gene. 2013 Jan 1;512(1):28-34
references.pmid: 23043934
references.citation: Hum Mutat. 2011 Jul;32(7):751-9
references.pmid: 21394827
references.citation: Atherosclerosis. 1993 Dec;104(1-2):153-8
references.pmid: 8141839
references.citation: J Biol Chem. 1995 Jun 16;270(24):14281-5
references.pmid: 7782284
references.citation: Clin Chim Acta. 2009 Mar;401(1-2):51-6
references.pmid: 19056372
references.citation: Crit Rev Clin Lab Sci. 2005;42(5-6):515-45
references.pmid: 16390683
references.citation: Mol Genet Metab. 2007 Apr;90(4):453-7
references.pmid: 17275380
references.citation: Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8686-91
references.pmid: 9671739
references.citation: Nutr Metab (Lond). 2012 Feb 21;9:14
references.pmid: 22353470
references.citation: Hum Mol Genet. 1993 Dec;2(12):2109-16
references.pmid: 8111381
references.citation: J Inherit Metab Dis. 1985;8 Suppl 1:88-92
references.pmid: 3930848
references.citation: Annu Rev Nutr. 2000;20:663-97
references.pmid: 10940349
references.citation: J Biol Chem. 1996 Nov 22;271(47):29945-52
references.pmid: 8939939
references.citation: Eur J Pediatr. 2009 Aug;168(8):983-9
references.pmid: 19066957
references.citation: Orphanet J Rare Dis. 2008 Jul 08;3:19
references.pmid: 18611256
references.citation: Eur J Pediatr. 1998 Jul;157(7):576-8
references.pmid: 9686820
references.citation: Science. 1992 Nov 6;258(5084):999-1001
references.pmid: 1439810
references.citation: J Biol Chem. 1999 Jan 29;274(5):3159-64
references.pmid: 9915855
references.citation: J Lipid Res. 2012 Mar;53(3):548-555
references.pmid: 22236406
references.citation: J Biol Chem. 2000 Sep 29;275(39):30372-7
references.pmid: 10893406
references.citation: Diagn Pathol. 2012 Jul 26;7(1):88
references.pmid: 22834788
references.citation: Mol Genet Metab. 2004 Feb;81(2):140-3
references.pmid: 14741197
references.citation: Cell Mol Life Sci. 2005 Jun;62(12):1372-8
references.pmid: 15818469
references.citation: Am J Hum Genet. 1995 Dec;57(6):1298-310
references.pmid: 8533758
references.citation: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references.pmid: 3344216
references.citation: Clin Genet. 2003 Feb;63(2):135-8
references.pmid: 12630961
references.citation: Atherosclerosis. 2007 Dec;195(2):e19-27
references.pmid: 17570373
references.citation: Biochemistry. 2007 Oct 30;46(43):12263-74
references.pmid: 17924655
references.citation: J Mol Biol. 1999 Jan 8;285(1):391-408
references.pmid: 9878414
references.citation: Diagn Pathol. 2011 Jun 17;6:54
references.pmid: 21682900
references.citation: Ann Hepatol. 2011 Apr-Jun;10(2):221-6
references.pmid: 21502686
references.citation: Atherosclerosis. 2012 May;222(1):158-66
references.pmid: 22417841
references.citation: Can Med Assoc J. 1985 Jan 1;132(1):41-4
references.pmid: 2981135
references.citation: Atherosclerosis. 2005 Jun;180(2):311-8
references.pmid: 15910857
references.citation: Adv Clin Chem. 2011;54:81-107
references.pmid: 21874758
references.citation: Gastroenterology. 1989 Sep;97(3):766-70
references.pmid: 2753336