%0 Journal Article
%T Quality Assessment of the Genetic Test for Familial Hypercholesterolemia in The Netherlands
%A Iris Kindt
%A Roeland Huijgen
%A Marieke Boekel
%A Kristiaan J. van der Gaag
%A Joep C. Defesche
%A John J. P. Kastelein
%A Peter de Knijff
%J Cholesterol
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/531658
%X Introduction. Familial hypercholesterolemia (FH) is an inherited disorder associated with a severely increased risk of cardiovascular disease. Although DNA test results in FH are associated with important medical and ethical consequences, data on accuracy of genetic tests is scarce. Methods. Therefore, we performed a prospective study to assess the overall accuracy of the DNA test used in the genetic cascade screening program for FH in The Netherlands. Individuals aged 18 years and older tested for one of the 5 most prevalent FH mutations, were included consecutively. DNA samples were analyzed by the reference and a counter-expertise laboratory following a standardized procedure. Results. 1003 cases were included. In the end, 317 (32%) carried an FH mutation, whereas in 686 (69%) samples no mutation was found. The overall accuracy of the reference laboratory was 99.8%, with two false positive results identified by the counter-expertise laboratory. Conclusion. The currently used mutation analysis is associated with a very low error rate. Therefore, we do not recommend routine use of duplicate testing. 1. Introduction The number of hereditary disorders for which a genetic test is available has increased from less than 200 in 1993 to more than 1,800 in 2009 [1]. Molecular genetic testing for these diseases raises a plethora of concerns, including the quality of test performance and interpretation of results [2]. Familial hypercholesterolemia (FH) is a condition that meets every criterion for genetic screening. FH is an autosomal codominant disorder of lipid metabolism with a prevalence of 1£¿:£¿500 in most Western countries [3]. Patients with FH have high plasma LDL cholesterol levels and an increased risk of coronary artery disease (CAD) [3, 4]. Statin therapy, intervening in the causal pathway of the disease, lowers CAD risk to a very significant extent in these individuals [5]. Defects in genes that code for proteins involved in hepatic clearance of low-density lipoprotein (LDL) cholesterol underlie the disorder [3]. In fact, more than a 1000 different mutations in the genes coding for the LDL-receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) are known to cause FH [6]. Such a causal mutation can be identified by DNA analysis in a varying percentage of patients with a clinical FH diagnosis, ranging from 20% to more than 90%, with highest rates of detection in children strictly selected for severe clinical FH [7¨C13]. Knowledge of the causal monogenetic mutation enables rapid screening of family members for
%U http://www.hindawi.com/journals/cholesterol/2013/531658/