Linked Life Data

8703016

Source:http://linkedlifedata.com/resource/pubmed/id/8703016

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
1996-10-10
pubmed:abstractText
Bernard-Soulier Syndrome (BSS) is a rare congenital bleeding disorder due to absent or decreased expression of the glycoprotein Ib-IX-V (GpIb-IX-V) receptor complex on the platelet surface. To date, only mutations in GpIbalpha or GpIX have been reported in patients with BSS. GpIbbeta differs from the other proteins in this receptor in that the gene is more complex, and an alternative form is expressed in cells of non-megakaryocytic lineage, including endothelial cells. It appears that the megakaryocytic and endothelial cell mRNA species are transcribed from different start sites and have different proximal promoter regions. We have identified a patient with BSS who has a deletion on one chromosome 22, resulting in velocardiofacial syndrome. The GpIbbeta gene has been mapped to this deleted (22q11.2) region of chromosome 22. The patient has greatly reduced levels of GpIbbeta mRNA and no detectable platelet GpIbbeta protein, suggesting that his BSS results from a mutation in his remaining GpIbbeta allele. Sequence analysis revealed that the coding region of GpIbbeta is normal, but the 5'-upstream region contains a C to G transversion at base -133 from the transcription start site used in megakaryocytes. The mutation changes a GATA consensus binding site, disrupts GATA-1 binding to the mutated site, and decreases promoter activity by 84%. Thus, in this patient, Bernard-Soulier syndrome results from a deletion of one copy of GpIbbeta and a mutated GATA binding site in the promoter of the remaining allele, resulting in decreased promoter function and GpIbbeta gene transcription.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22076-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8703016-Alleles, pubmed-meshheading:8703016-Base Sequence, pubmed-meshheading:8703016-Bernard-Soulier Syndrome, pubmed-meshheading:8703016-Binding Sites, pubmed-meshheading:8703016-Blotting, Southern, pubmed-meshheading:8703016-Blotting, Western, pubmed-meshheading:8703016-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:8703016-Chromosomes, Human, Pair 3, pubmed-meshheading:8703016-DNA, pubmed-meshheading:8703016-DNA-Binding Proteins, pubmed-meshheading:8703016-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:8703016-Erythroid-Specific DNA-Binding Factors, pubmed-meshheading:8703016-GATA1 Transcription Factor, pubmed-meshheading:8703016-Humans, pubmed-meshheading:8703016-Molecular Sequence Data, pubmed-meshheading:8703016-Platelet Glycoprotein GPIb-IX Complex, pubmed-meshheading:8703016-Point Mutation, pubmed-meshheading:8703016-Polymerase Chain Reaction, pubmed-meshheading:8703016-Promoter Regions, Genetic, pubmed-meshheading:8703016-RNA, Messenger, pubmed-meshheading:8703016-Restriction Mapping, pubmed-meshheading:8703016-Transcription Factors, pubmed-meshheading:8703016-Transfection
pubmed:year
1996
pubmed:articleTitle
Identification of a mutation in a GATA binding site of the platelet glycoprotein Ibbeta promoter resulting in the Bernard-Soulier syndrome.
pubmed:affiliation
Cardeza Foundation for Hematologic Research, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't