G to T transversion at position +5 of a splice donor site causes skipping of the preceding exon in the type III procollagen transcripts of a patient with Ehlers-Danlos syndrome type IV.

Details

Serval ID
serval:BIB_7D6FDFAFD2DD
Type
Article: article from journal or magazin.
Collection
Publications
Title
G to T transversion at position +5 of a splice donor site causes skipping of the preceding exon in the type III procollagen transcripts of a patient with Ehlers-Danlos syndrome type IV.
Journal
Journal of Biological Chemistry
Author(s)
Lee B., Vitale E., Superti-Furga A., Steinmann B., Ramirez F.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
1991
Volume
266
Number
8
Pages
5256-5259
Language
english
Abstract
We identified a splicing mutation in a patient with Ehlers-Danlos syndrome type IV, a heritable connective tissue disorder associated with dysfunctions of type III collagen. The mutation was first localized in the patient's type III procollagen mRNA by amplifying the reverse transcribed product in several overlapping fragments using the polymerase chain reaction. Amplified products spanning exon 24-26 sequences displayed two distinct fragments, one of normal size and the other lacking the 99 base pairs of exon 25. Sequencing of amplified genomic products identified a G to T transversion at position +5 of the splice donor site of intron 25 in one of the patient's procollagen III genes. Expression of allelic minigene constructs correlated the T for G substitution with skipping of exon 25 sequences. Like previously characterized splicing mutations in other collagen genes, lowering the temperature at which the patient's fibroblasts were incubated nearly abolished exon skipping. As a part of this study, we also identified a highly polymorphic, intronic DNA sequence whose different allelic forms can be detected easily by the polymerase chain reaction technique.
Keywords
Alleles, Autoradiography, Base Sequence, DNA/genetics, Ehlers-Danlos Syndrome/genetics, Exons, Guanine, Humans, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Procollagen/genetics, RNA Splicing, RNA, Messenger/genetics, Thymine, Transcription, Genetic
Pubmed
Create date
14/03/2011 16:14
Last modification date
20/08/2019 14:38
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