An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia.
Atherosclerosis
; 216(1): 139-45, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21310417
ABSTRACT
OBJECTIVE:
Familial hypercholesterolemia (FH) is an inborn disorder of lipid metabolism characterised by elevated plasma concentrations of low-density lipoprotein cholesterol and total cholesterol. This imbalance results in accelerated atherosclerosis and premature coronary heart disease. The early identification and treatment of FH patients is extremely important because it leads to significant reduction of both coronary morbidity and mortality. FH is transmitted in an autosomal dominant manner and associated predominantly with mutations in the genes encoding the low-density lipoprotein receptor (LDLR) and its ligand apolipoprotein B (APOB). To date, more than 1000 sequence variants have been described in the LDLR gene. In marked contrast to LDLR, only one APOB mutation is prevalent in Europe. METHODS ANDRESULTS:
The aim of this study was, on the basis of data obtained by the molecular genetic analysis of 1945 Czech FH probands, to propose, generate, and validate a new diagnostic tool, an APEX (Arrayed Primer EXtension)-based genotyping DNA microarray called the FH chip. The FH chip contains the APOB mutation p.Arg3527Gln, all 89 LDLR point mutations and small DNA rearrangements detected in Czech FH patients, and 78 mutations frequent in other European and Asian FH populations. The validation phase revealed the sensitivity and specificity of this platform, 100% and 99.1%, respectively.CONCLUSIONS:
This FH chip is a rapid, reproducible, specific, and cost-effective tool for genotyping, and in combination with MLPA (multiple ligation-dependent probe amplification) represents a reliable molecular genetic protocol for the large-scale screening of FH mutations in the Czech population.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas B
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Receptores de LDL
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Análise Mutacional de DNA
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Testes Genéticos
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Programas de Rastreamento
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Análise de Sequência com Séries de Oligonucleotídeos
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Perfilação da Expressão Gênica
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Hiperlipoproteinemia Tipo II
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Mutação
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Atherosclerosis
Ano de publicação:
2011
Tipo de documento:
Article