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http://purl.uniprot.org/citations/15890894http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15890894http://www.w3.org/2000/01/rdf-schema#comment"

Background

Patients with familial hypercholesterolemia (FH) have a high risk of premature cardiovascular disease (PCVD). Mutations in the LDL receptor (LDLR) gene and the R3500Q mutation in the apolipoprotein B (APOB) gene are known to cause FH, but lack of high-throughput methods makes routine genetic diagnosis difficult. The objective of this work was to develop a DNA array for large-scale identification of mutant LDLR alleles.

Methods

We developed a low-density oligonucleotide microarray to identify 118 DNA sequence variations (117 for the LDLR gene and 1 for the APOB gene). We verified specificity and sensitivity by analyzing 1180 previously sequenced DNA samples, and conducted a blind study screening 407 Spanish patients with a clinical diagnosis of FH.

Results

The DNA array confirmed the previous genotyping results in almost all cases. In the blind study, the microarray detected at least 1 mutation in 51% of the patients for whom clinical diagnosis was classified as certain according to Dutch FH-MEDPED criteria; it also identified mutations in 37% of those with a diagnosis of probable/possible FH, thus giving a definite diagnosis. Patients harboring null mutations had shorter PCVD-free survival times and higher relative risk of PCVD than patients with a missense mutation.

Conclusions

The proposed DNA array allows large-scale population screening and provides molecular information regarding mutation type and its correlation with clinical severity of FH, which can be used to develop therapeutic strategies."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.org/dc/terms/identifier"doi:10.1373/clinchem.2004.045203"xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Lopez M."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Martinez A."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Alonso R."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Jimenez E."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Artieda M."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Castillo S."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Mata P."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Mozas P."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Pocovi M."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Tejedor D."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Simon L."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/author"Tejedor M.T."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/name"Clin Chem"xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/pages"1137-1144"xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/title"Reliable low-density DNA array based on allele-specific probes for detection of 118 mutations causing familial hypercholesterolemia."xsd:string
http://purl.uniprot.org/citations/15890894http://purl.uniprot.org/core/volume"51"xsd:string
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