Source:http://linkedlifedata.com/resource/pubmed/id/10668928
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2000-2-25
|
| pubmed:abstractText |
In the present study, we have characterized a unique splice donor G to A substitution in the moderately conserved + 5 position in intron 10 of the low-density lipoprotein (LDL) receptor gene. In two Danish families, carriers of the 1592 + 5G --> A mutation display a clinical phenotype ranging from healthy normocholesterolemic persons to classical heterozygous familial hypercholesterolemia (FH) patients. Reverse transcription-polymerase chain reaction (RT-PCR) of RNA from Epstein Barr virus (EBV)-transformed lymphoblasts obtained from members of both families demonstrated abnormal splicing generating two aberrant mRNAs due to either alternative splicing and skipping of exon 10 or activation of a cryptic splice site in intron 10 inserting 66 intronic base pairs. These abnormally spliced mRNAs were predicted to encode two abnormal receptor proteins containing an in-frame deletion of 75 amino acids and an insertion of 22 novel amino acids, respectively. Results obtained by immunofluorescence staining, flow cytometry, and confocal microscopy of transfected Chang and COS-7 cells expressing normal and mutant LDL receptors were compatible with nearly complete retention of the mutant proteins in the endoplasmic reticulum. Quantitative measurements of LDL receptor mRNAs from EBV-transformed lymphoblasts, however, did not reveal any significant differences in variant mRNA contents between mutation carriers in the families that could be related to degree of hypercholesterolemia.
|
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0009-9163
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
56
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
378-88
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10668928-Adult,
pubmed-meshheading:10668928-Animals,
pubmed-meshheading:10668928-Cell Line,
pubmed-meshheading:10668928-DNA Mutational Analysis,
pubmed-meshheading:10668928-Flow Cytometry,
pubmed-meshheading:10668928-Fluorescent Antibody Technique,
pubmed-meshheading:10668928-Heterozygote,
pubmed-meshheading:10668928-Humans,
pubmed-meshheading:10668928-Hyperlipoproteinemia Type II,
pubmed-meshheading:10668928-Lipids,
pubmed-meshheading:10668928-Male,
pubmed-meshheading:10668928-Microscopy, Confocal,
pubmed-meshheading:10668928-Pedigree,
pubmed-meshheading:10668928-Point Mutation,
pubmed-meshheading:10668928-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:10668928-RNA Splicing,
pubmed-meshheading:10668928-Receptors, LDL,
pubmed-meshheading:10668928-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10668928-Transfection
|
| pubmed:year |
1999
|
| pubmed:articleTitle |
Normolipidemia and hypercholesterolemia in persons heterozygous for the same 1592 + 5G --> A splice site mutation in the low-density lipoprotein receptor gene.
|
| pubmed:affiliation |
Department of Medicine and Cardiology, Aarhus Amtssygehus University Hospital, Denmark. hkjensen@dadlnet.dk
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|