RGD Reference Report - Compound heterozygosity of the GPIbalpha gene associated with Bernard-Soulier syndrome. - Rat Genome Database

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Compound heterozygosity of the GPIbalpha gene associated with Bernard-Soulier syndrome.

Authors: Gonzalez-Manchon, C  Larrucea, S  Pastor, AL  Butta, N  Arias-Salgado, EG  Ayuso, MS  Parrilla, R 
Citation: Gonzalez-Manchon C, etal., Thromb Haemost. 2001 Dec;86(6):1385-91.
RGD ID: 10450843
Pubmed: PMID:11776304   (View Abstract at PubMed)

We report the molecular genetic analysis of the Bernard-Soulier syndrome (BSS) phenotype in two related patients showing absence of glycoprotein (GP) Ibalpha and detectable amounts of GPIX on the platelet surface, and a truncated form of GPIbalpha in solubilized platelets and plasma. They both were compound heterozygotes for the GPIbalpha gene: a maternal allele with a T insertion at position 1418 causing a translational frameshift and premature polypeptide termination, and a paternal allele with a T715A substitution chan-ino Cys209 to Ser. Heterozygotes for either one of these mutations were asymptomatic. Transient transfection of cells coexpressing GPIbbeta and GPIX failed to detect surface expression of the GPIbalpha mutants. Cells transfected with [1418insT]GPIbalpha-cDNA showed a truncated protein of the predicted size in both cell lysate and conditioned medium, indicating the inability of the mutant protein to anchor the plasma membrane. In contrast. transfection of [T715A]GPIbalpha-cDNA yield a mutated protein barely detectable in the cell lysate and absent in the medium, indicating that the loss of Cys209 renders GPIbalpha more vulnerable to proteolysis and unable to undergo the normal secretory pathway. Our findings indicate that the additive effects of both mutations are responsible for the BSS phenotype of the patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Bernard-Soulier syndrome  IAGP 10450843DNA:missense mutation and nonsense mutation: :p.C209S (715T>A) (human)RGD 
Bernard-Soulier syndrome  ISOGP1BA (Homo sapiens)10450843; 10450843DNA:missense mutation and nonsense mutation: :p.C209S (715T>A) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gp1ba  (glycoprotein Ib platelet subunit alpha)

Genes (Mus musculus)
Gp1ba  (glycoprotein 1b, alpha polypeptide)

Genes (Homo sapiens)
GP1BA  (glycoprotein Ib platelet subunit alpha)


Additional Information