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Identification and biochemical analysis of a novel APOB mutation that causes autosomal dominant hypercholesterolemia.

Title: Identification and biochemical analysis of a novel APOB mutation that causes autosomal dominant hypercholesterolemia.
Authors: Thomas, ERA
Atanur, SS
Norsworthy, PJ
Encheva, V
Snijders, AP
Game, L
Vandrovcova, J
Siddiq, A
Seed, M
Soutar, AK
Aitman, TJ
Item Type: Journal Article
Abstract: Patients with autosomal dominant hypercholesterolemia (ADH) have a high risk of developing cardiovascular disease that can be effectively treated using statin drugs. Molecular diagnosis and family cascade screening is recommended for early identification of individuals at risk, but up to 40% of families have no mutation detected in known genes. This study combined linkage analysis and exome sequencing to identify a novel variant in exon 3 of APOB (Arg50Trp). Mass spectrometry established that low-density lipoprotein (LDL) containing Arg50Trp APOB accumulates in the circulation of affected individuals, suggesting defective hepatic uptake. Previously reported mutations in APOB causing ADH have been located in exon 26. This is the first report of a mutation outside this region causing this phenotype, therefore, more extensive screening of this large and highly polymorphic gene may be necessary in ADH families. This is now feasible due to the high capacity of recently available sequencing platforms.
Issue Date: Sep-2013
Date of Acceptance: 7-May-2013
URI: http://hdl.handle.net/10044/1/93261
DOI: 10.1002/mgg3.17
ISSN: 2324-9269
Publisher: Wiley Open Access
Start Page: 155
End Page: 161
Journal / Book Title: Molecular Genetics and Genomic Medicine
Volume: 1
Issue: 3
Copyright Statement: © 2013 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: APOB
autosomal dominant hypercholesterolemia
exome sequencing
familial hypercholesterolemia
mass spectrometry
APOB
autosomal dominant hypercholesterolemia
exome sequencing
familial hypercholesterolemia
mass spectrometry
0304 Medicinal and Biomolecular Chemistry
0604 Genetics
1103 Clinical Sciences
Publication Status: Published
Conference Place: United States
Online Publication Date: 2013-06-13
Appears in Collections:Department of Metabolism, Digestion and Reproduction



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