Disease relevance of COL3A1

• Mutations in the COL3A1 gene that encodes the chains of type III procollagen result in the vascular form of Ehlers-Danlos syndrome (EDS), EDS type IV, if they alter the sequence in the triple-helical domain [1].
• A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms [2].
• The results indicated that mutations in the gene for type III procollagen (COL3A1) are not a common cause of either intracranial artery aneurysms or cervical artery dissections [3].
• Exclusion of mutations in the gene for type III collagen (COL3A1) as a common cause of intracranial aneurysms or cervical artery dissections: results from sequence analysis of the coding sequences of type III collagen from 55 unrelated patients [3].
• Ehlers-Danlos syndrome type IV with a unique point mutation in COL3A1 and familial phenotype of myocardial infarction without organic coronary stenosis [4].

High impact information on COL3A1

• BACKGROUND: Ehlers-Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1) [5].
• Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a >80% reduction in COL1A1 mRNA, and a >70% reduction in COL3A1 mRNA in both cell types [6].
• Although other fibrillar collagen-gene mutations that lead to allele instability or failure to incorporate proalpha-chains into trimers-and that thus reduce the amount of mature molecules produced-result in clinically apparent phenotypes, no such mutations have been identified in COL3A1 [1].
• Mutations in the COL3A1 gene have been implicated as a cause of type IV Ehlers-Danlos syndrome, a disease leading to aortic rupture in early adult life [7].
• In fibroblasts from the father, approximately two-fifths of the COL3A1 alleles carried the deletion, but only 10% of the COL3A1 alleles in white blood cells were of the mutant species [8].

Chemical compound and disease context of COL3A1

• Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother [9].
• Single-strand conformation polymorphism (SSCP) analysis of the COL3A1 gene detects a mutation that results in the substitution of glycine 1009 to valine and causes severe Ehlers-Danlos syndrome type IV [10].
• A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An unaffected family member is mosaic for the mutation [11].
• 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 [12].

Biological context of COL3A1

• The human type II collagen gene, COL2A1, has been assigned to chromosome 12, the type III gene, COL3A1, to chromosome 2, and one of the type IV genes, COL4A1, to chromosome 13 [13].
• Amplified cDNAs prepared from lymphoblastoid cells were used to identify previously characterized heterozygous mutations in the COL1A1 and COL1A2 genes from two patients with osteogenesis imperfecta and in the COL3A1 gene from a patient with the Ehlers-Danlos syndrome type IV [14].
• Physical mapping by PFGE localizes the COL3A1 and COL5A2 genes to a 35-kb region on human chromosome 2 [15].
• Therefore, the COL3A1 and COL5A2 genes appear to exist as a gene cluster on chromosome 2 [15].
• Inheritance of an RNA splicing mutation (G+ 1 IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV [16].

Anatomical context of COL3A1

• Collagen types I and III, coded by COL1A1/COL1A2 and COL3A1 genes, are the major fibrillar collagens produced by fibroblasts, including cardiac fibroblasts of the adult heart [17].
• The proband was heterozygous for a 2-kb deletion in COL3A1, while her father was mosaic for the same deletion in somatic and germ cells [8].
• Mutations in the COL3A1 gene result in the Ehlers-Danlos syndrome type IV and alterations in the size and distribution of the major collagen fibrils of the dermis [18].
• Association between COL3A1 collagen gene exon 31 polymorphism and risk of floppy mitral valve/mitral valve prolapse [19].
• We conclude that variants in the COL3A1 gene, the product of which is a vessel-wall protein and platelet ligand, modulate the risk of coronary artery disease and could also modulate the response to antithrombotic therapy [20].

Associations of COL3A1 with chemical compounds

• Mutation analysis revealed a point mutation in the COL3A1 gene that substituted glycine for aspartate at amino acid position 877 [4].
• Activation of COL3A1 promoter activity by cyclosporine [21].

Other interactions of COL3A1

• Thus, in contrast to mutations in genes that encode the dominant protein of a tissue (e.g., COL1A1 and COL2A1), in which "null" mutations result in phenotypes milder than those caused by mutations that alter protein sequence, the phenotypes produced by these mutations in COL3A1 overlap with those of the vascular form of EDS [1].
• Recently, several mutations in three other collagen genes (COL2A1, COL3A1, and COL4A5) have been found in probands with genetic diseases involving tissues rich in these collagens [22].
• This mutation is analogous to mutations causing exon skipping in the major collagen genes, COL1A1, COL1A2, and COL3A1, identified in several cases of osteogenesis imperfecta and EDS type IV [23].
• We report here on the complete structure of the human COL3A1 and COL5A2 genes [24].
• The reduction in the production of procollagen chains was shown to result from a combination of IFN-gamma-induced inhibition of the transcription rates of the COL1A1 and COL3A1 genes and destabilization of the corresponding transcripts [25].

Analytical, diagnostic and therapeutic context of COL3A1

• By using light, transmission, and scanning electron microscopy, we examined skin biopsies from 22 individuals with EDS type IV in whom the COL3A1 mutations had been identified [18].
• No disease-causing mutations were found in an extended sequence analysis of the COL3A1 gene in patients with sCAD [26].
• The polymorphisms of exon 31 and exon 52 of the collagen type III-alpha1 gene (COL3A1) were identified by polymerase chain reaction (PCR)-based restriction analysis [19].
• RT-PCR experiments demonstrated that 14% stretch up-regulated levels of mRNA for COL3A1 gene (type III collagen) but did not increase the expression of COL1A1 gene (type I collagen) in valve interstitial cells [27].
• The gene for the alpha 1 (III) chain of type III collagen, COL3A1, has been previously mapped to human chromosome 2q24.3-q31 by in situ hybridization [28].

References