High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in the Netherlands: Identification and characterization of eight novel mutations
| Autor: | 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 |
|---|---|
| Přispěvatelé: | Vascular Medicine, Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine, Human Genetics |
| Rok vydání: | 2011 |
| Předmět: |
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 |
| Zdroj: | Human mutation, 32(11), 1290-1298. Wiley-Liss Inc. |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.21578 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text