Source:http://linkedlifedata.com/resource/pubmed/id/10950936
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2000-10-13
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| pubmed:abstractText |
Gaucher disease, the most common glycolipid storage disease, can be caused by a large variety of mutations. We report here the identification and characterization of a novel mutation in the human glucocerebrosidase gene, IVS 8 (-11delC) (-14T>A), in two siblings with Gaucher disease type I which occurs within the 3' end of intron 8. Both siblings were compound heterozygotes for the IVS 8 (-11delC) (-14T>A) mutation and for the c.626 G>C (R170P) substitution within exon 6. No mRNA species carrying the IVS 8 (-11delC) (-14T>A) mutation were detected by RT-PCR analysis of the RNA extracted from the patients' fibroblasts. To study the possible effects of the IVS 8 (-11delC) (-14T>A) sequence alteration on the splicing of the proximal exon 9, we have established an in vitro system generating a minigene carrying the genomic region of human glucocerebrosidase spanning from exon 8 to exon 10. Transfections into the human Hep3B cell line of the wild-type construct resulted in the expression of mRNA with the glucocerebrosidase exons correctly spliced. On the contrary, transfections of the construct carrying the IVS 8 (-11delC) (-14T>A) mutation resulted in the expression of mRNA with an 11-bp insertion located between the end of exon 8 and the beginning of exon 9. These results indicated that the 5243T>A substitution created a new 3' splice site 11 bp upstream of the wild-type one, leading to the incorporation into the mRNA of these extra 11 bases. Moreover, the new 3' splice site created by this 5243T>A transversion was preferred over the wild-type one in 100% of cases. The in vitro studies suggest that, in the patients, the 11-bp inclusion causes a shift in the reading frame with the generation of a stop codon after codon 388 which undergoes early degradation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1079-9796
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:volume |
26
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
171-6
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10950936-Adult,
pubmed-meshheading:10950936-Amino Acid Sequence,
pubmed-meshheading:10950936-Base Sequence,
pubmed-meshheading:10950936-Exons,
pubmed-meshheading:10950936-Female,
pubmed-meshheading:10950936-Gaucher Disease,
pubmed-meshheading:10950936-Glucosylceramidase,
pubmed-meshheading:10950936-Heterozygote,
pubmed-meshheading:10950936-Humans,
pubmed-meshheading:10950936-Introns,
pubmed-meshheading:10950936-Italy,
pubmed-meshheading:10950936-Male,
pubmed-meshheading:10950936-Molecular Sequence Data,
pubmed-meshheading:10950936-Nuclear Family,
pubmed-meshheading:10950936-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10950936-Sequence Deletion,
pubmed-meshheading:10950936-Transfection,
pubmed-meshheading:10950936-Tumor Cells, Cultured
|
| pubmed:year |
2000
|
| pubmed:articleTitle |
Functional characterization of the novel mutation IVS 8 (-11delC) (-14T>A) in the intron 8 of the glucocerebrosidase gene of two Italian siblings with Gaucher disease type I.
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| pubmed:affiliation |
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, 34012, Italy.
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| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
|