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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
43
|
| pubmed:dateCreated |
1998-11-17
|
| pubmed:abstractText |
A novel C to A mutation in the sterol 27-hydroxylase gene (CYP27) was identified by sequencing amplified CYP27 gene products from a patient with cerebrotendinous xanthomatosis (CTX). The mutation changed the adrenodoxin cofactor binding residue 362Arg to 362Ser (CGT 362Arg to AGT 362Ser), and was responsible for deficiency in the sterol 27-hydroxylase activity, as confirmed by expression of mutant cDNA into COS-1 cells. Quantitative analysis showed that the expression of CYP27 gene mRNA in the patient represented 52.5% of the normal level. As the mutation occurred at the penultimate nucleotide of exon 6 (-2 position of exon 6-intron 6 splice site) of the gene, we hypothesized that the mutation may partially affect the normal splicing efficiency in exon 6 and cause alternative splicing elsewhere, which resulted in decreased transcript in the patient. Transfection of constructed minigenes, with or without the mutation, into COS-1 cells confirmed that the mutant minigene was responsible for a mRNA species alternatively spliced at an activated cryptic 5' splice site 88 bp upstream from the 3' end of exon 6. Our data suggest that the C to A mutation at the penultimate nucleotide of exon 6 of the CYP27 gene not only causes the deficiency in the sterol 27-hydroxylase activity, but also partially leads to alternative pre-mRNA splicing of the gene. To our knowledge, this is the first report regarding effects on pre-mRNA splicing of a mutation at the -2 position of a 5' splice site.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/CYP27A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP27A1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0006-2960
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
27
|
| pubmed:volume |
37
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
15050-6
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9790667-Alternative Splicing,
pubmed-meshheading:9790667-Amino Acid Substitution,
pubmed-meshheading:9790667-Animals,
pubmed-meshheading:9790667-Arginine,
pubmed-meshheading:9790667-COS Cells,
pubmed-meshheading:9790667-Cytochrome P-450 CYP27A1,
pubmed-meshheading:9790667-Cytochrome P-450 Enzyme System,
pubmed-meshheading:9790667-DNA, Complementary,
pubmed-meshheading:9790667-Enzyme Activation,
pubmed-meshheading:9790667-Humans,
pubmed-meshheading:9790667-Male,
pubmed-meshheading:9790667-Middle Aged,
pubmed-meshheading:9790667-Point Mutation,
pubmed-meshheading:9790667-RNA Precursors,
pubmed-meshheading:9790667-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:9790667-Serine,
pubmed-meshheading:9790667-Steroid Hydroxylases,
pubmed-meshheading:9790667-Transcription, Genetic,
pubmed-meshheading:9790667-Transfection,
pubmed-meshheading:9790667-Xanthomatosis, Cerebrotendinous
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity.
|
| pubmed:affiliation |
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Japan.
|
| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
|