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| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/17211858 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17211858 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17211858 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in the COL1A1 and COL1A2 genes, encoding the proalpha1 and 2 chains of type I collagen, cause osteogenesis imperfecta (OI) or Ehlers-Danlos syndrome (EDS) arthrochalasis type. Although the majority of missense mutations in the collagen type I triple helix affect glycine residues in the Gly-Xaa-Yaa repeat, few nonglycine substitutions have been reported. Two arginine-to-cysteine substitutions in the alpha1(I)-collagen chain are associated with classic EDS [R134C (p.R312C)] or autosomal dominant Caffey disease with mild EDS features [R836C (p.R1014C)]. Here we show alpha1(I) R-to-C substitutions in three unrelated patients who developed iliac or femoral dissection in early adulthood. In addition, manifestations of classic EDS in Patient 1 [c.1053C>T; R134C (p.R312C); X-position] or osteopenia in Patients 2 [c.1839C>T; R396C (p.R574C); Y-position] and 3 [c.3396C>T; R915C (p.R1093C); Y-position] are seen. Dermal fibroblasts from the patients produced disulfide-bonded alpha1(I)-dimers in approximately 20% of type I collagen, which were efficiently secreted into the medium in case of the R396C and R915C substitution. Theoretical stability calculations of the collagen type I heterotrimer and thermal denaturation curves of monomeric mutant alpha1(I)-collagen chains showed minor destabilization of the collagen helix. However, dimers were shown to be highly unstable. The R134C and R396C caused delayed procollagen processing by N-proteinase. Ultrastructural findings showed collagen fibrils with variable diameter and irregular interfibrillar spaces, suggesting disturbed collagen fibrillogenesis. Our findings demonstrate that R-to-C substitutions in the alpha1(I) chain may result in a phenotype with propensity to arterial rupture in early adulthood. This broadens the phenotypic range of nonglycine substitutions in collagen type I and has important implications for genetic counseling and follow-up of patients carrying this type of mutation."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.20455"xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.20455"xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "De Paepe A."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "De Paepe A."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Lapiere C.M."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Lapiere C.M."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Malfait F."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Malfait F."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Symoens S."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Symoens S."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Coucke P."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Coucke P."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Hermanns-Le T."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Hermanns-Le T."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "De Backer J."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "De Backer J."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Sakalihasan N."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/author | "Sakalihasan N."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/name | "Hum. Mutat."xsd:string |
| http://purl.uniprot.org/citations/17211858 | http://purl.uniprot.org/core/name | "Hum. Mutat."xsd:string |