Linked Life Data

11470490

Source:http://linkedlifedata.com/resource/pubmed/id/11470490

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2001-7-25
pubmed:abstractText
Gap junction channels formed by the connexin43 protein are considered to play crucial roles in development and function because they allow the direct cell-to-cell exchange of molecules that mediate multiple signaling events. Previous results have shown that connexin43 channels are intricately gated by phosphorylation and that disruption of this regulation gives rise to severe heart malformations and defects of laterality in human, chick and frog. Here we report the identification of connexin43 gene mutations that represent a minor population of connexin43 alleles, which could be reliably detected by using denaturing gradient gel electrophoresis (DGGE) to visualize normal and mutant DNAs that were separately sequenced. In contrast, sequencing of total PCR products without DGGE-pre-selection failed to consistently identify these mutations. Forty-six controls and 20 heart transplant recipients were examined in this study. In the latter group, 14 children had hypoplastic left heart syndrome (HLHS) in which connexin43 gene defects were detected in eight. The remaining six transplant patients with HLHS and all controls showed no defects. All eight HLHS children with gene defects had the same four substitutions: two that were silent polymorphisms, and two that were missense, replacing arginine codons at positions 362 and 376 with codons for glutamines. All four of these substitutions are identical to the nucleotide sequence of the connexin43 pseudogene, suggesting the possibility of an illicit recombination. A breakpoint region was identified 5' to the mutation site in a 63bp domain that is 100% identical in the gene and pseudogene. Results from in vitro phosphorylation indicate that the absence of arginines 362 and 376 completely abolishes phosphorylation in the connexin43 channel regulation domain suggesting a possible mechanism for the pathologies associated with HLHS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
479
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-86
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11470490-Base Sequence, pubmed-meshheading:11470490-Child, pubmed-meshheading:11470490-Codon, pubmed-meshheading:11470490-Connexin 43, pubmed-meshheading:11470490-DNA Mutational Analysis, pubmed-meshheading:11470490-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:11470490-Female, pubmed-meshheading:11470490-Formamides, pubmed-meshheading:11470490-Gap Junctions, pubmed-meshheading:11470490-Heart Transplantation, pubmed-meshheading:11470490-Humans, pubmed-meshheading:11470490-Hypoplastic Left Heart Syndrome, pubmed-meshheading:11470490-Infant, pubmed-meshheading:11470490-Infant, Newborn, pubmed-meshheading:11470490-Male, pubmed-meshheading:11470490-Molecular Sequence Data, pubmed-meshheading:11470490-Mutation, pubmed-meshheading:11470490-Mutation, Missense, pubmed-meshheading:11470490-Peptides, pubmed-meshheading:11470490-Phosphorylation, pubmed-meshheading:11470490-Protein Structure, Tertiary, pubmed-meshheading:11470490-Recombination, Genetic, pubmed-meshheading:11470490-Single-Blind Method, pubmed-meshheading:11470490-Temperature, pubmed-meshheading:11470490-Time Factors, pubmed-meshheading:11470490-Urea
pubmed:year
2001
pubmed:articleTitle
Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE).
pubmed:affiliation
Department of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.