A lack of platelet progenitor cells (megakaryocytes) in the bone marrow leads to a reduced production and release of blood platelets into the blood stream. This deficiency can occur in isolation (like in the Congenital Amegakaryocytic Thrombocytopenia = CAMT) or in association with additional aberrations, esp. upon the skeleton. If the radius bones of both forearms are missing (and both thumbs are present), the syndrome is referred to as Thrombocytopenia-absent-radii (TAR)-syndrome. It is a very rare disorder (1-2 cases in a million births). Children with TAR-syndrome have a very low platelet count, particularly during the first two years of life and often present with a variety of very small punctual bleedings (petechiae). Later, despite platelet counts rising, patients remain thrombocytopenic and have a tendency to bleed more often or for a longer period of time.
The genetic cause for TAR syndrome is still very poorly understood. Recently, we could detect a loss of a small portion of the DNA (genetic material) on a chromosome in all of 30 patients with TAR syndrome analyzed (microdeletion). As some of the unaffected parents carry this deletion too, there must be an additional factor to coin the complete feature of TAR syndrome. Several months ago we identified two small changes in the sequence of the DNA within the microdeletion that only occur in patients with TAR-syndrome. My group is currently working to better understand how the combination of microdeletion and the small DNA changes can cause TAR-syndrome.
One focus of our laboratory is to identify and further characterize the genetic and molecular mechanisms that provoke the lack of platelets in patients affected with TAR syndrome.