What are the genetic changes related to gray platelet syndrome ?
Gray platelet syndrome can be caused by mutations in the NBEAL2 gene. Little is known about the protein produced from this gene. It appears to play a role in the formation of alpha-granules, which are sacs inside platelets that contain growth factors and other proteins that are important for blood clotting and wound healing. In response to an injury that causes bleeding, the proteins stored in alpha-granules help platelets stick to one another to form a plug that seals off damaged blood vessels and prevents further blood loss.  Mutations in the NBEAL2 gene disrupt the normal production of alpha-granules. Without alpha-granules, platelets are unusually large and fewer in number than usual (macrothrombocytopenia). The abnormal platelets also appear gray when viewed under a microscope, which gives this condition its name. A lack of alpha-granules impairs the normal activity of platelets during blood clotting, increasing the risk of abnormal bleeding. Myelofibrosis is thought to occur because the growth factors and other proteins that are normally packaged into alpha-granules leak out into the bone marrow. The proteins lead to fibrosis that affects the bone marrow's ability to make new blood cells.  Some people with gray platelet syndrome do not have an identified mutation in the NBEAL2 gene. In these individuals, the cause of the condition is unknown.