Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_3496C46C20B6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study.
Journal
Swiss medical weekly
Author(s)
Maurer F., Pradervand S., Guilleret I., Nanchen D., Maghraoui A., Chapatte L., Bojkowska K., Bhuiyan Z.A., Jacquemont N., Harshman K., Mooser V.
ISSN
1424-3997 (Electronic)
ISSN-L
0036-7672
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
146
Pages
w14326
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
We aimed to identify familial hypercholesterolaemia mutation carriers among participants to the Lausanne Institutional Biobank (BIL). Our experimental workflow was designed as a proof-of-concept demonstration of the resources and services provided by our integrated institutional clinical research support platform.
Familial hypercholesterolaemia was used as a model of a relatively common yet often underdiagnosed and inadequately treated Mendelian disease. Clinical and laboratory information was extracted from electronic hospital records. Patients were selected using elevated plasma cholesterol levels (total cholesterol ≥7.5 mM or low-density lipoprotein cholesterol ≥5 mM), premature coronary artery disease status and age (18-60 yr) as main inclusion criteria. LDLR, APOB and PCSK9 were analysed by high-throughput DNA sequencing. The most relevant mutations were confirmed by Sanger sequencing.
Of 23 737 patients contacted by the BIL, 17 760 individuals consented to participate and 13 094 wished to be recontacted if there were findings requiring clinical action. Plasma cholesterol records were available for 5111 participants, of whom 94 were selected for genetic screening. Twenty-five of the tested patients presented with premature coronary artery disease while 69 had no such diagnosis. Seven heterozygous carriers of eight rare coding missense variants were identified. Three mutations were pathogenic (APOB p.R3527Q) or likely pathogenic (LDLR p.C27W, LDLR p.P526S) for hypercholesterolaemia, while the others were either benign or of unknown significance. One patient was a double heterozygote for variants APOB p.R3527Q and LDLR p.P526S.
This work illustrates how clinical and translational research can benefit from a dedicated platform integrating both a hospital-based biobank and a data support team.

Keywords
Adolescent, Adult, Apolipoproteins B/genetics, Biological Specimen Banks, Cholesterol/blood, Cholesterol, LDL/blood, Coronary Artery Disease/epidemiology, Female, Humans, Hyperlipoproteinemia Type II/blood, Hyperlipoproteinemia Type II/genetics, Male, Medical Records, Middle Aged, Mutation/genetics, Polymerase Chain Reaction, Proprotein Convertase 9/genetics, Receptors, LDL/genetics, Switzerland/epidemiology, Young Adult
Pubmed
Open Access
Yes
Create date
12/08/2016 9:19
Last modification date
20/08/2019 14:21
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