Molecular characterization of familial hypercholesterolemia in Spain
| Autor: | Diego Tejedor, Estibaliz Olano-Martin, Lourdes Palacios, Antonio Martínez, Laura Grandoso, Nerea Cuevas, Marianne Stef |
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| Rok vydání: | 2012 |
| Předmět: |
Heterozygote
DNA Copy Number Variations Apolipoprotein B Familial hypercholesterolemia medicine.disease_cause Severity of Illness Index Hyperlipoproteinemia Type II Exon medicine Humans Genetic Predisposition to Disease Copy-number variation Apolipoproteins B Oligonucleotide Array Sequence Analysis Genetics Analysis of Variance Mutation biology Gene Expression Profiling PCSK9 Homozygote Serine Endopeptidases Exons medicine.disease Phenotype Receptors LDL Spain LDL receptor biology.protein Kexin lipids (amino acids peptides and proteins) Proprotein Convertases Proprotein Convertase 9 Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 221:137-142 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2011.12.021 |
| Popis: | Familial hypercholesterolemia (FH), characterized by isolated elevation of plasmatic low-density lipoprotein (LDL) cholesterol and premature coronary heart disease (CHD), is associated with mutations in three major genes: LDL receptor ( LDLR) , apolipoprotein B ( APOB ) and proprotein convertase subtilisin/kexin 9 ( PCSK9) . We have analyzed 5430 Spanish index cases and 2223 relatives since 2004 with LIPOchip ® genetic diagnostic platform, a microarray for the detection of Spanish common mutations in these three genes, including copy number variation (CNV) in LDLR , followed by sequencing analysis of the coding regions of LDLR and exon 26 of APOB , when the result is negative. Samples were received from hospitals of all around Spain. The preferred clinical criterion to diagnose FH was Dutch Lipid Clinic Network (DLCN) score. Our results show that there is a broad spectrum of mutations in the LDLR gene in Spain since about 400 different mutations were detected, distributed along almost the whole LDLR gene. Mutations in APOB (mainly p.Arg3527Gln) covered 6.5% of positive cases and only one PCSK9 mutation was detected. We found correlation between more severe mutations and the clinical diagnosis but also that 28% of FH patients harboring mutations do not have a definite clinical diagnosis. This study analyzes the mutation spectrum in Spain, remarks the importance of genetic diagnosis of FH patients, as well as the cascade screening, and shows how it is being carried out in Spain. |
| Databáze: | OpenAIRE |
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