Gray platelet syndrome ... (Gray platelet syndrome) - Gen NBEAL2.

Gray platelet syndrome (SPG) is a rare bleeding disorder characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and appearance typically gray platelet. Affected individuals develop bruises easily and have an increased risk of epistaxis. In addition, these individuals may exhibit abnormally heavy or prolonged bleeding after surgery, dental work, or minor trauma. Often, women with gray platelet syndrome have menometrorragia. These bleeding problems are usually mild to moderate. However, in some affected individuals they have been fatal. Another common feature of this disease is myelofibrosis. Scarring associated with myelofibrosis damages bone marrow, preventing produce enough blood cells. Other organs, particularly the spleen, offset the production of blood cells. This process often leads to splenomegaly.

Gray platelet syndrome may be due to mutations in the gene NBEAL2, located on the short arm of chromosome 3 (3p21.31). Although the function of the protein encoded by this gene is not clear, it appears to be critical for normal development of the platelet. Platelets are formed from precursor cells known as megakaryocytes. Inside these cells, it is believed that NBEAL2 protein plays a role in the development of alpha granules, which are the most abundant components of platelets. Alpha granules contain growth factors and other proteins that are important for blood clotting and wound healing. In response to an injury which causes bleeding, proteins stored in the alpha granules help platelets to stick together to facilitate sealing of damaged and prevent loss of blood vessels.

They have identified at least 35 mutations in the gene responsible NBEAL2 gray platelet syndrome. Mutations in the gene NBEAL2 alter the normal production of alpha granules megakaryocytes, causing macrothrombocytopenia. Abnormal platelets also have a gray appearance when viewed under a microscope. Alpha granules deficiency impairs platelet agglutination in response to injury, increasing the risk of abnormal bleeding. Meanwhile, it is believed that myelofibrosis occurs because the growth factors and other proteins which normally are assembled in alpha granules, filtered bone marrow. Proteins lead to fibrosis that affects the ability of the bone marrow to produce new blood cells. Some people with gray platelet syndrome have identified a mutation in the gene NBEAL2. In these individuals, the cause of the disease is unknown.

When gray platelet syndrome is due to genetic mutations NBEAL2 has an autosomal recessive inheritance pattern, meaning that two copies of the gene in each cell have mutations. 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. This disease can also be inherited in an autosomal dominant pattern, which means that a copy of an altered gene in each cell is sufficient to express the alteration. Often, an affected person inherits the disease from an affected parent. Work is being done to determine which gene or genes are associated with autosomal dominant form of gray platelet syndrome.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with gray platelet (SPG) syndrome by complete PCR amplification of exons NBEAL2 gene, and subsequent sequencing.

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).