Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV.

Details

Serval ID
serval:BIB_0A4F0712FA2E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV.
Journal
American Journal of Human Genetics
Author(s)
Lee B., D'Alessio M., Vissing H., Ramirez F., Steinmann B., Superti-Furga A.
ISSN
0002-9297 (Print)
ISSN-L
0002-9297
Publication state
Published
Issued date
1991
Volume
48
Number
3
Pages
511-517
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. Publication Status: ppublish
Abstract
Ehlers-Danlos syndrome type IV (EDS IV) is an autosomal dominant condition characterized by extreme fragility of skin, blood vessels, intestine, gravid uterus, and lungs. The phenotype is accounted for by mutations affecting the integrity and/or synthesis of the precursor procollagen molecules of type III collagen. In this article, we report the elucidation of the molecular defect in an EDS IV patient whose type III collagen was previously found to be structurally abnormal. We utilized PCR in a two-step process involving first the localization of the mutation in the mRNA and then the characterization of the defect in the gene. The results established the patient's heterozygosity for a genomic deletion of about 7.5 kb which eliminates 1,026 nucleotides of coding sequences in the message. The mutation arose as a result of an exon-to-intron recombination. The deleted segment extends from the 13th nucleotide of exon 9 to within a DNA sequence of intron 24, which is composed of a series of dinucleotide repeats. Using PCR, we tested the polymorphic nature of this DNA element on several unrelated individuals. Analysis of amplified genomic products of 45 chromosomes recognized at least four distinct allelic forms that display frequencies ranging from 5% to 61%. Mendelian segregation of three of the four alleles was established by the same method in a 3-generation family.
Keywords
Alleles, Amino Acid Sequence, Base Sequence, Cells, Cultured, Chromosome Deletion, Collagen/genetics, DNA/chemistry, Ehlers-Danlos Syndrome/diagnosis, Ehlers-Danlos Syndrome/genetics, Exons, Gene Frequency, Humans, Introns, Molecular Sequence Data, Nucleotides/genetics, Pedigree, Polymorphism, Genetic, RNA, Messenger/chemistry, Recombination, Genetic, Repetitive Sequences, Nucleic Acid, Restriction Mapping
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Create date
14/03/2011 17:14
Last modification date
03/03/2018 13:33
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