title: Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors: Fabienne
authors: F
authors: Maurer
authors: Service of Clinical Research Support, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland, and Genomic Technologies Facility, Centre for Integrative Genomics, University of Lausanne, Switzerland.
authors: Sylvain
authors: S
authors: Pradervand
authors: Service of Clinical Research Support, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors: Isabelle
authors: I
authors: Guilleret
authors: Department of Ambulatory Care and Community Medicine, University of Lausanne, Switzerland.
authors: David
authors: D
authors: Nanchen
authors: Service of Clinical Research Support, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors: Ali
authors: A
authors: Maghraoui
authors: Service of Clinical Research Support, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors: Laurence
authors: L
authors: Chapatte
authors: Genomic Technologies Facility, Centre for Integrative Genomics, University of Lausanne, Switzerland.
authors: Karolina
authors: K
authors: Bojkowska
authors: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors: Zahurul Alam
authors: ZA
authors: Bhuiyan
authors: Service of Clinical Research Support, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors: Nathalie
authors: N
authors: Jacquemont
authors: Genomic Technologies Facility, Centre for Integrative Genomics, University of Lausanne, Switzerland.
authors: Keith
authors: K
authors: Harshman
authors: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Service of Clinical Research Support, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Service of Biomedicine.
authors: Vincent
authors: V
authors: Mooser
mesh_terms: D000293:Adolescent; D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D018070:Biological Specimen Banks; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000453:epidemiology; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D000071449:Proprotein Convertase 9 / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D013557:Switzerland / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; C573412:LDLR protein, human; D011973:Receptors, LDL; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9