Scientific background:

Summary: The gene ITGB3 encodes a major component of the glycoprotein IIb-IIIa complex, which binds fibrinogen and controls platelet clutting. Mutations result in autosomal recessive Glanzmann thrombasthenia, and polymorphisms account for alloimmune thrombocytopenia of the newborn.

Gene: The gene spans about 60kb. Only one splice variant is known that consists of 15 exons all of them coding.

Interpretation: The originally published sequence differs from our currently used database in codon numbering. In the original publication, translation starts at codon -26. for this reason, published mutations might differ from currently used codone numbers.
   The platelet-specific alloantigen system Pl(A) is based on a missense mutation at codon position 59, which was originally described as L33P. This mutation is the one most frequently implicated in syndromes of immune-mediated platelet destruction, particularly neonatal alloimmune thrombocytopenia and posttransfusion purpura.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Rosenberg N et al. (1997) Glanzmann thrombasthenia caused by an 11.2-kb deletion in the glycoprotein IIIa (beta3) is a second mutation in Iraqi Jews that stemmed from a distinct founder.
Wang R et al. (1997) Truncation of the cytoplasmic domain of beta3 in a variant form of Glanzmann thrombasthenia abrogates signaling through the integrin alpha(IIb)beta3 complex.
Ferrer M et al. (1998) Truncation of glycoprotein (GP) IIIa (616-762) prevents complex formation with GPIIb: novel mutation in exon 11 of GPIIIa associated with thrombasthenia.
Newman PJ et al. (1991) The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel.
Peretz H et al. (2006) Molecular diversity of Glanzmann thrombasthenia in southern India: new insights into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin (ITGA2B, ITGB3).
Fitzgerald LA et al. (1987) Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to "integrin".
Newman PJ et al. (1989) The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing.
Santoso S et al. (1993) The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2).
Newman PJ et al. (1994) Nomenclature of human platelet alloantigens: a problem with the HPA system?
Nair S et al. (2005) Mutations in GPIIIa molecule as a cause for Glanzmann thrombasthenia in Indian patients.
Kannan M et al. (2008) Carrier detection in Glanzmann thrombasthenia: comparison of flow cytometry and Western blot with respect to DNA mutation.