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.
- 1 March 1991
- journal article
- Vol. 48 (3) , 511-7
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.This publication has 28 references indexed in Scilit:
- Brittle bones - fragile molecules: disorders of collagen gene structure and expressionPublished by Elsevier ,2002
- Identification of the Molecular Defect in a Family with Spondyloepiphyseal DysplasiaScience, 1989
- Molecular defects of type III procollagen in Ehlers-Danlos syndrome type IVHuman Genetics, 1989
- Cloning and analysis of the 5′ portion of the human type-III procollagen gene (COL3A1)Gene, 1989
- Nucleotide and amino acid sequences of the entire human α1 (III) collagenNucleic Acids Research, 1989
- Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: Correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the moleculeBiochemical and Biophysical Research Communications, 1988
- Detection of restriction fragment length polymorphisms at the centromeres of human chromosomes by using chromosome-specific alpha satellite DNA probes: implications for development of centromere-based genetic linkage maps.Proceedings of the National Academy of Sciences, 1986
- Enzymatic Amplification of β-Globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell AnemiaScience, 1985
- Human alpha 1(III) and alpha 2(V) procollagen genes are located on the long arm of chromosome 2.Proceedings of the National Academy of Sciences, 1985
- Hypervariable ‘minisatellite’ regions in human DNANature, 1985