Trp207Gly in platelet glycoprotein Ibalpha is a novel mutation that disrupts the connection between the leucine-rich repeat domain and the disulfide loop structure and causes Bernard-Soulier syndrome.
J Thromb Haemost
; 5(2): 378-86, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17083647
ABSTRACT
BACKGROUND:
Bernard-Soulier syndrome (BSS) is a severe inherited bleeding disorder that is caused by a defect in glycoprotein (GP)Ib-IX-V complex, the platelet membrane receptor for von Willebrand factor. PATIENTS The diagnosis of BSS was made in two members of a Bukharian Jewish family who had life-long thrombocytopenia associated with mucocutaneous bleeding manifestations. METHODS ANDRESULTS:
Flow cytometry and Western blot analyses showed only trace amounts of GPIb and GPIX on the patients' platelets. Sequence analysis of the GPIbalpha gene revealed a homozygous T > G transversion at nucleotide 709 predicting Trp207Gly substitution in the mature protein. Introduction of the mutation into a mammalian expression construct abolished the surface expression of GPIbalpha in transfected baby hamster kidney cells. The crystal structure of the N-terminus of GPIbalpha (PDB 1SQ0) indicates that Trp207 is completely buried and located in a disulfide loop structure that interacts with the leucine-rich repeat (LRR) domain.CONCLUSION:
A novel mutation, Trp207Gly, causes BSS and predicts disruption of the interaction between a disulfide loop and the LRR domain that is essential for the integrity of GPIbalpha structure.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Bernard-Soulier
/
Pliegue de Proteína
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Complejo GPIb-IX de Glicoproteína Plaquetaria
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Mutación Missense
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Leucina
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adolescent
/
Child
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Female
/
Humans
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Israel