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: Berna Seker Yilmaz, Neslihan Onenli Mungan, Enza Di Leo, Lucia Magnolo, Lucia Artuso, Isabella Bernardis, Gokhan Tumgor, Deniz Kor, Patrizia Tarugi
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 452 Pg. 185-90 (Jan 15 2016) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 26612772 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Apolipoproteins B

Topics

• Apolipoproteins B (genetics)
• Female
• Humans
• Hypobetalipoproteinemia, Familial, Apolipoprotein B (blood, diet therapy, genetics)
• Infant
• Mutation, Missense
• Pedigree
• Polymerase Chain Reaction
• Sequence Analysis, DNA
• Turkey