Linked Life Data

17211858

Source:http://linkedlifedata.com/resource/pubmed/id/17211858

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-4-16
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
387-95
pubmed:meshHeading
pubmed-meshheading:17211858-Adolescent, pubmed-meshheading:17211858-Adult, pubmed-meshheading:17211858-Amino Acid Substitution, pubmed-meshheading:17211858-Arginine, pubmed-meshheading:17211858-Base Sequence, pubmed-meshheading:17211858-Bone Diseases, Metabolic, pubmed-meshheading:17211858-Collagen, pubmed-meshheading:17211858-Collagen Type I, pubmed-meshheading:17211858-Collagen Type III, pubmed-meshheading:17211858-Cysteine, pubmed-meshheading:17211858-Ehlers-Danlos Syndrome, pubmed-meshheading:17211858-Female, pubmed-meshheading:17211858-Femoral Artery, pubmed-meshheading:17211858-Humans, pubmed-meshheading:17211858-Iliac Artery, pubmed-meshheading:17211858-Male, pubmed-meshheading:17211858-Molecular Sequence Data, pubmed-meshheading:17211858-Mutation, Missense, pubmed-meshheading:17211858-Protein Structure, Secondary, pubmed-meshheading:17211858-RNA, Messenger, pubmed-meshheading:17211858-Rupture, Spontaneous
pubmed:year
2007
pubmed:articleTitle
Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood.
pubmed:affiliation
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't