Linked Life Data

9367795

Source:http://linkedlifedata.com/resource/pubmed/id/9367795

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-9
pubmed:abstractText
We examined the type I collagen synthesized by cultured dermal fibroblasts from a patient affected with osteogenesis imperfecta (OI) type IV. Both normal and abnormal trimers were produced. The mutant collagen molecules were excessively modified intracellularly, had a melting temperature 4 degrees C lower than the control, were secreted at a reduced rate, and underwent delayed processing to mature alpha chains.Molecular investigations identified a G --> A transition in one COL1A2 allele, resulting in a Gly922 --> Ser substitution in the alpha2(I) chain. The proband's mutation was demonstrated to arise "de novo" by the absence of the mutant allele restriction enzyme pattern from parental genomic DNA.We analyzed the insoluble extracellular matrix deposited by long-term cultured fibroblasts from our patient and from a previously described unrelated individual who carries an identical substitution. In both cases, the mutant chain constituted 10-15% of the total alpha chains deposited.We also present here the first detailed comparison of phenotype between unrelated OI patients with an identical collagen mutation. These two patients are both Caucasian females, ages 8 and 9 years, each diagnosed as type IV OI by the Sillence classification. They have a similar phenotype including moderate skeletal fragility with several femur fractures, dentinogenesis imperfecta, wormian bone, and reduced height and weight. We conclude that this phenotype is related both to the location of this mutation and to the similar extent of matrix incorporation by the mutant chains. Molecular and biochemical studies of unrelated individuals with identical amino acid substitutions in type I collagen resulting in either similar or dissimilar clinical outcomes will make a significant contribution to identifying the factors involved in the modulation of the OI phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1077-3150
pubmed:author
pubmed:copyrightInfo
Copyright 1997 Academic Press.
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Phenotypic comparison of an osteogenesis imperfecta type IV proband with a de novo alpha2(I) Gly922 --> Ser substitution in type I collagen and an unrelated patient with an identical mutation.
pubmed:affiliation
Department of Biochemistry "A. Castellani", University of Pavia, Pavia, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Case Reports, Research Support, Non-U.S. Gov't