Glanzmann thrombasthenia (Glanzmann thrombasthenia) - Genes ITGA2B and ITGB3.
Glanzmann's thrombasthenia is an inherited disorder of platelet aggregation, which is characterized by prolonged or spontaneous bleeding, mild to moderate intensity. The severity and frequency of bleeding may vary among affected individuals, even in the same family. Spontaneous bleeding tends to be less frequent with age.
Signs and clinical symptoms associated with this disease can include easy bruising presence, epistaxis, bleeding gums, petechiae and bruising. This disease can also cause prolonged bleeding after injury, trauma or surgery, including dental procedures. In the women affected, alteration can cause heavy menstrual bleeding and increased risk of excessive bleeding during pregnancy and childbirth. In addition, about a quarter of people with Glanzmann thrombasthenia have gastrointestinal bleeding. In rare cases, affected individuals may have intracranial hemorrhage or hemarthrosis.
This process is due to mutations in genes ITGA2B, located on the long arm of chromosome 17 (17q21.31) and ITGB3, also located on the long arm of chromosome 17 (17q21.32). These genes, encoding two subunits of a receptor protein called integrin which is abundant in the surface of platelets (glycoprotein platelet alpha-IIb and IIIa platelet glycoprotein, respectively). During clot formation, the ?IIb?3 integrin helps platelets to adhere.
They have identified at least 200 mutations in the gene ITGA2B and 130 mutations in the gene ITGB3 in people with Glanzmann thrombasthenia. Mutations in these genes result in a deficiency of functional integrin ?IIb?3, preventing the binding of fibrinogen and other proteins. Consequently, platelets can not be grouped to form a blood clot, leading to prolonged bleeding.
Described three subtypes of this disease according to the amount of ?IIb?3 integrin is available: type I, type II and type variant. People with type I, the most common type, are less than 5% of normal levels of integrin ?IIb?3; People with type II are between 5% and 20% of normal levels of integrin ?IIb?3; and those with the variant type have adequate levels of integrin ?IIb?3 integrin but produce only nonfunctional. Some people with Glanzmann have identified a mutation in the gene or ITGA2B ITGB3 gene. The cause of the disease is unknown in these individuals.
Glanzmann's thrombasthenia is inherited as an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for the disease is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Glanzmann thrombasthenia, by complete PCR amplification of the exons of ITGA2B and ITGB3, respectively, and subsequent sequencing genes.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).