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Your search keyword '"Joep C. Defesche"' showing total 2 results
Start Over Author "Joep C. Defesche" Publisher hindawi limited
2 results on '"Joep C. Defesche"'

1. High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in the Netherlands: Identification and characterization of eight novel mutations

Author

John J.P. Kastelein, Jan Albert Kuivenhoven, Frank Peelman, M. Mahdi Motazacker, Alinda W. M. Schimmel, Jorge Peter, Adriaan G. Holleboom, Joep C. Defesche, G. Kees Hovingh, Erik S.G. Stroes, Vascular Medicine, Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine, and Human Genetics

Subjects
Adult, Male, Heterozygote, medicine.medical_specialty, Biology, medicine.disease_cause, Phosphatidylcholine-Sterol O-Acyltransferase, chemistry.chemical_compound, Corneal Opacity, High-density lipoprotein, Lecithin Cholesterol Acyltransferase Deficiency, Internal medicine, Chlorocebus aethiops, Prevalence, Genetics, medicine, Animals, Humans, Fish-Eye Disease, Hypoalphalipoproteinemia, Genetics (clinical), Aged, Netherlands, Mutation, Cholesterol, Cholesterol, HDL, Lecithin Acyltransferase Deficiency, Genetic Variation, nutritional and metabolic diseases, Middle Aged, medicine.disease, Endocrinology, chemistry, Child, Preschool, COS Cells, Female, lipids (amino acids, peptides, and proteins), Phosphatidylcholine—sterol O-acyltransferase, Lipoprotein
Abstract

Lecithin:cholesterol acyltransferase (LCAT) is crucial to the maturation of high-density lipoprotein (HDL). Homozygosity for LCAT mutations underlies rare disorders characterized by HDL-cholesterol (HDL-c) deficiency while heterozygotes have half normal HDL-c levels. We studied the prevalence of LCAT mutations in referred patients with low HDL-c to better understand the molecular basis of low HDL-c in our patients. LCAT was sequenced in 98 patients referred for HDL-c T (p.E134D), c.403T>A (p.Y135N), c.964C>T (p.R322C), c.296G>C (p.W99S), c.736G>T (p.V246F), c.802C>T (p.R268C), c.945G>A (p.W315X), c.1012C>T (p.L338F), and c.1039C>T (p.R347C)--were shown to be functional through in vitro characterization. The effect of several mutations on the core protein structure was studied by a three-dimensional (3D) model. Unlike previous reports, functional mutations in LCAT were found in 29% of patients with low HDL-c, thus constituting a common cause of low HDL-c in referred patients in The Netherlands

Published
2011
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2. Quality Assessment of the Genetic Test for Familial Hypercholesterolemia in The Netherlands

Author

Marieke Boekel, Kristiaan J. van der Gaag, John J.P. Kastelein, Iris Kindt, Roeland Huijgen, Peter de Knijff, and Joep C. Defesche

Subjects
Pediatrics, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Article Subject, business.industry, Quality assessment, Endocrinology, Diabetes and Metabolism, Organic Chemistry, Dna test, Hematology, Disease, Familial hypercholesterolemia, medicine.disease, Test (assessment), lcsh:RC666-701, Mutation (genetic algorithm), Internal Medicine, Mutation testing, Medicine, business, Prospective cohort study, Research Article
Abstract

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.

Published
2013

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