Linked Life Data

10216092

Source:http://linkedlifedata.com/resource/pubmed/id/10216092

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1999-5-18
pubmed:abstractText
Bernard-Soulier syndrome is an uncommon bleeding disorder caused by a quantitative or qualitative defect in the platelet glycoprotein (GP)Ib/IX complex. The complex is composed of four subunits, GPIbalpha, GPIbbeta, GPIX, and GPV. Here we describe the molecular basis of a novel Bernard-Soulier syndrome variant in a patient in whom GPIbalpha and GPIX were undetectable on the platelet surface. DNA sequence analysis showed normal sequence for GPIbalpha, GPIX, and GPV. The GPIbbeta gene has been mapped to the 22q11.2 region of chromosome 22 which was deleted from one chromosome of this patient. There was a single nucleotide deletion within the codon for Ala 80 in GPIbbeta within the other allele. This mutation causes a translational frame shift that encodes for 86 altered amino acids and predicts a premature stop 15 amino acids short of the length of the wild-type protein. Transient coexpression of the mutant GPIbbeta in 293T cells with wild-type GPIbalpha and GPIX resulted in the surface expression of GPIbalpha, but the absence of GPIX. Moreover, when a plasmid encoding the wild-type GPIbbeta was transiently transfected into Chinese hamster ovary cells stably expressing GPalpha, which retain the capacity to reexpress GPIX, there was a significant increase in the surface expression of GPIX. In contrast, when the mutant GPIbbeta was transiently transfected into these cells, GPIX was not reexpressed on the plasma surface. Thus, a deletion of one copy of GPIbbeta and a single nucleotide deletion in the codon for Ala 80 within the remaining GPIbbeta allele causes the Bernard-Soulier phenotype through an interaction of GPIbbeta with GPIX resulting in the absence of GPIbalpha on the plasma membrane. The interaction of GPIbbeta with GPIX is essential for the functional expression of GPIbalpha.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2968-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10216092-Adolescent, pubmed-meshheading:10216092-Alanine, pubmed-meshheading:10216092-Amino Acid Sequence, pubmed-meshheading:10216092-Animals, pubmed-meshheading:10216092-Base Sequence, pubmed-meshheading:10216092-Bernard-Soulier Syndrome, pubmed-meshheading:10216092-CHO Cells, pubmed-meshheading:10216092-Chromosome Mapping, pubmed-meshheading:10216092-Chromosomes, Human, Pair 22, pubmed-meshheading:10216092-Codon, pubmed-meshheading:10216092-Codon, Terminator, pubmed-meshheading:10216092-Cricetinae, pubmed-meshheading:10216092-Frameshift Mutation, pubmed-meshheading:10216092-Gene Deletion, pubmed-meshheading:10216092-Humans, pubmed-meshheading:10216092-Male, pubmed-meshheading:10216092-Platelet Glycoprotein GPIb-IX Complex, pubmed-meshheading:10216092-Recombinant Proteins, pubmed-meshheading:10216092-Sequence Deletion, pubmed-meshheading:10216092-Transfection
pubmed:year
1999
pubmed:articleTitle
The critical interaction of glycoprotein (GP) IBbeta with GPIX-a genetic cause of Bernard-Soulier syndrome.
pubmed:affiliation
Blood Research Institute, the Blood Center of Southeastern Wisconsin, and the Departments of Medicine, Pediatrics, and Pathology, Medical College of Wisconsin, Milwaukee, WI, USA. dkenny@rcsi.ie
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Case Reports, Research Support, Non-U.S. Gov't