Linked Life Data

17568391

Source:http://linkedlifedata.com/resource/pubmed/id/17568391

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-23
pubmed:abstractText
Congenital diaphragmatic hernia (CDH) is a common, life threatening birth defect. Although there is strong evidence implicating genetic factors in its pathogenesis, few causative genes have been identified, and in isolated CDH, only one de novo, nonsense mutation has been reported in FOG2 in a female with posterior diaphragmatic eventration. We report here that the homozygous null mouse for the Pdgfralpha gene has posterolateral diaphragmatic defects and thus is a model for human CDH. We hypothesized that mutations in this gene could cause human CDH. We sequenced PDGFRalpha and FOG2 in 96 patients with CDH, of which 53 had isolated CDH (55.2%), 36 had CDH and additional anomalies (37.5%), and 7 had CDH and known chromosome aberrations (7.3%). For FOG2, we identified novel sequence alterations predicting p.M703L and p.T843A in two patients with isolated CDH that were absent in 526 and 564 control chromosomes respectively. These altered amino acids were highly conserved. However, due to the lack of available parental DNA samples we were not able to determine if the sequence alterations were de novo. For PDGFRalpha, we found a single variant predicting p.L967V in a patient with CDH and multiple anomalies that was absent in 768 control chromosomes. This patient also had one cell with trisomy 15 on skin fibroblast culture, a finding of uncertain significance. Although our study identified sequence variants in FOG2 and PDGFRalpha, we have not definitively established the variants as mutations and we found no evidence that CDH commonly results from mutations in these genes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1018-4813
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
950-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17568391-Amino Acid Sequence, pubmed-meshheading:17568391-Animals, pubmed-meshheading:17568391-Chromosomes, Human, Pair 15, pubmed-meshheading:17568391-Cohort Studies, pubmed-meshheading:17568391-DNA-Binding Proteins, pubmed-meshheading:17568391-Disease Models, Animal, pubmed-meshheading:17568391-Embryo, Mammalian, pubmed-meshheading:17568391-Genetic Variation, pubmed-meshheading:17568391-Hernia, Diaphragmatic, pubmed-meshheading:17568391-Humans, pubmed-meshheading:17568391-Mice, pubmed-meshheading:17568391-Mice, Inbred C57BL, pubmed-meshheading:17568391-Molecular Sequence Data, pubmed-meshheading:17568391-Receptor, Platelet-Derived Growth Factor alpha, pubmed-meshheading:17568391-Sequence Analysis, DNA, pubmed-meshheading:17568391-Transcription Factors, pubmed-meshheading:17568391-Trisomy
pubmed:year
2007
pubmed:articleTitle
Candidate genes for congenital diaphragmatic hernia from animal models: sequencing of FOG2 and PDGFRalpha reveals rare variants in diaphragmatic hernia patients.
pubmed:affiliation
Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural