Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France.

Journal of Lipid Research
René WintjensFabienne Dufernez

Abstract

Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH-associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found...Continue Reading

References

Jun 5, 1988·Journal of Molecular Biology·D J Barlow, J M Thornton
Aug 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·D GaffneyC J Packard
Dec 25, 2000·The Journal of Biological Chemistry·J BorénT L Innerarity
Mar 8, 2002·American Journal of Epidemiology·June E EichnerBerrit C Stroehla
Aug 17, 2004·Clinical Chemistry·Amanda J WhitfieldJohn R Burnett
Oct 4, 2005·Journal of Medical Genetics·D Baralle, M Baralle
Jul 6, 2006·Trends in Biochemical Sciences·Danny M HattersKarl H Weisgraber
Jul 18, 2006·Nucleic Acids Research·Vijaya ParthibanDietmar Schomburg
Nov 22, 2007·Clinical Genetics·M VarretC Boileau
Jan 1, 1997·Methods in Enzymology·E A Merritt, D J Bacon
Dec 25, 2008·Journal of Lipid Research·Robert W MahleyYadong Huang
Mar 31, 2009·Journal of Pediatric Gastroenterology and Nutrition·Pascale BenlianJean Philippe Girardet
May 19, 2009·The Journal of Pediatrics·Ornella GuardamagnaStefano Bertolini
May 29, 2009·Neurogenetics·Hervé CrehaletDominique Bozon
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 24, 2010·European Journal of Human Genetics : EJHG·Alice Marques-PinheiroMathilde Varret
Sep 3, 2010·Human Mutation·Marie MarduelJean-Pierre Rabès
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jianglei ChenJianjun Wang
Mar 13, 2012·European Heart Journal·Mohammad Mahdi MotazackerSigrid W Fouchier
Nov 16, 2013·Human Molecular Genetics·Ana Catarina AlvesMafalda Bourbon
Nov 26, 2013·Atherosclerosis·Zuhier AwanJacques Genest
Jan 1, 2014·Archives of Cardiovascular Diseases·Michel Farnier
Feb 6, 2014·Molecular Genetics & Genomic Medicine·Ellen R A ThomasTimothy J Aitman
Jul 6, 2014·Journal of Medical Genetics·Marta FutemaSteve E Humphries
Jul 19, 2014·Circulation Research·Sigrid W FouchierG Kees Hovingh
May 15, 2015·European Heart Journal·Yuichi J Shimada, Christopher P Cannon
May 29, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ana Margarida MedeirosMafalda Bourbon

❮ Previous
Next ❯

Citations

May 21, 2016·Nature Reviews. Endocrinology·Katrina L EllisGerald F Watts
Nov 11, 2016·Molecular Genetics and Metabolism Reports·Trond P LerenKnut Erik Berge
Mar 8, 2019·Current Opinion in Lipidology·Ana C AlvesMafalda Bourbon
Dec 6, 2017·The Open Cardiovascular Medicine Journal·Omran Mohammed RashidiZuhier Ahmed Awan
Mar 23, 2017·Current Opinion in Lipidology·Sebastiano CalandraStefano Bertolini
Jul 19, 2018·Journal of the Endocrine Society·Sirawit Ittisoponpisan, Alessia David
Jan 24, 2017·Concussion·Jane McDevitt, Evgeny Krynetskiy
Nov 6, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Roeland HuijgenA David Marais
Nov 30, 2018·Praxis·Manuela SchöbStefan Bilz
May 11, 2021·Current Atherosclerosis Reports·A D Marais
Jun 1, 2021·Atherosclerosis·Yara Abou KhalilMathilde Varret

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.