Type

Report

Authors

Dermot Kenny
Niamh Moran
Ségolène Claeyssens
Robert Combrié
Paquita Nurden
Alan Nurden
Andrew Hillmann

Subjects

Biochemistry

Topics
transfection amino acid substitution blood alleles male cell line molecular sequence data blood platelets physiology bernard soulier syndrome humans genotype adolescent mutation female pedigree chemistry amino acid sequence cloning molecular platelet glycoprotein gpib ix complex genetics protein structure tertiary sequence deletion

A novel hemizygous Bernard-Soulier Syndrome (BSS) mutation in the amino terminal domain of glycoprotein (GP)Ibbeta--platelet characterization and transfection studies. (2002)

Abstract Glycoprotein (GP) Ib-V-IX is a unique adhesion receptor complex on platelets. Mutations in GPIbalpha, Ibbeta, and IX can lead to the rare bleeding disorder, Bernard-Soulier Syndrome (BSS). Here, we report a novel hemizygous variant of BSS in which Pro29 in one GPIbbeta allele is substituted by a Leu (GPIbbeta:P29L). Fluoresence in situ hybridisation revealed that the 22q11 locus was deleted from the homologous chromosome. The pedigree was determined and revealed inheritance of the GPIbbeta:P29L allele from the father. Flow cytometry with a range of antibodies detected no expression of GPIb-V-IX on the surface of the patient's platelets. Western blotting revealed an absence of GPIbalpha and GPIbbeta from platelet lysates. Co-expression of GPIbbeta:P29L with normal GPIbalpha and GPIX in a heterologous cell system confirmed that the mutant subunit did not support surface expression of the complex. Interestingly, residual expression of GPIbbeta:P29L anchored in the plasma membrane alone was now seen. This novel BSS mutation expressed in heterologous cells is in agreement with recent in vitro evidence that the correct conformation of the amino terminal region of GPIbbeta is required for normal expression of the intact receptor complex.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Dermot Kenny, Niamh Moran, Ségolène Claeyssens, Robert Combrié, Paquita Nurden, Alan Nurden, Andrew Hillmann

Experts in our system

1
Dermot Kenny
Royal College of Surgeons in Ireland
 
2
Niamh Moran
Royal College of Surgeons in Ireland
Total Publications: 50