title: Homozygous familial hypobetalipoproteinemia: A Turkish case carrying a missense mutation in apolipoprotein B.
abstract: The autosomal co-dominant disorder familial hypobetalipoproteinemia (FHBL) may be due to mutations in the APOB gene encoding apolipoprotein B (apoB), the main constituent peptide of chylomicrons, very low and low density lipoproteins. We describe an 11month-old child with failure to thrive, intestinal lipid malabsorption, hepatic steatosis and severe hypobetalipoproteinemia, suggesting the diagnosis of homozygous FHBL, abetalipoproteinemia (ABL) or chylomicron retention disease (CMRD). The analysis of candidate genes showed that patient was homozygous for a variant (c.1594 C>T) in the APOB gene causing arginine to tryptophan conversion at position 505 of mature apoB (Arg505Trp). No mutations were found in a panel of other potential candidate genes for hypobetalipoproteinemia. In vitro studies showed a reduced secretion of mutant apoB-48 with respect to the wild-type apoB-48 in transfected McA-RH7777 cells. The Arg505Trp substitution is located in the βα1 domain of apoB involved in the lipidation of apoB mediated by microsomal triglyceride transfer protein (MTP), the first step in VLDL and chylomicron formation. The patient's condition improved in response to a low fat diet supplemented with fat-soluble vitamins. Homozygosity for a rare missense mutation in the βα1 domain of apoB may be the cause of both severe hypobetalipoproteinemia and intestinal lipid malabsorption.
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Cukurova University, Adana, Turkey. Electronic address: berna_seker@yahoo.co.uk.
authors.forename: Berna Seker
authors.initials: BS
authors.lastname: Yilmaz
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Cukurova University, Adana, Turkey. Electronic address: munganhno@gmail.com.
authors.forename: Neslihan Onenli
authors.initials: NO
authors.lastname: Mungan
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Centre for Genome Research, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: enzadileo76@libero.it.
authors.forename: Enza
authors.initials: E
authors.lastname: Di Leo
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: lucillamag@libero.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Magnolo
authors.affiliation: Centre for Genome Research, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: lucia.artuso@unimore.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Artuso
authors.affiliation: Centre for Genome Research, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: isabella.bernardis@unimore.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bernardis
authors.affiliation: Department of Pediatric Gastroenterology, Cukurova University, Adana, Turkey. Electronic address: gtumgor74@yahoo.com.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Tumgor
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Cukurova University, Adana, Turkey. Electronic address: dozonur@yahoo.com.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kor
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Centre for Genome Research, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: tarugi@unimore.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
mesh_terms: D001055:Apolipoproteins B / Q000235:genetics*; D005260:Female; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000097:blood / Q000178:diet therapy / Q000235:genetics*; D007223:Infant; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014421:Turkey
chemical_list: D001055:Apolipoproteins B
keywords: Apolipoprotein B; Familial hypobetalipoproteinemia; Hepatic steatosis; Lipid malabsorption; Missense mutation