Submitted April 22, 2009
Accepted June 5, 2009
Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation
Claudio Graziano*, Simona Carone, Emanuele Panza, Flora Marino, Pamela Magini, Giovanni Romeo, Andrea Pession, and Marco Seri
U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, Universita degli Studi di Bologna, Bologna, Italy
Oncologia ed Ematologia Pediatrica "Lalla Seragnoli", Policlinico Sant'Orsola-Malpighi, Bologna, Italy
* Corresponding author; email: claudio.graziano{at}unibo.it.
Hereditary thrombocythemia is a rare autosomal dominant disorder, caused by mutations in either the thrombopoietin gene (TPO) or its receptor c-MPL. TPO mutations described so far lead to thrombopoietin overproduction through increased translation of m-RNA. Unilateral transverse reduction limb defects are usually sporadic and generally thought to be caused by vascular disruptions. Reports of inherited unilateral limb defects are extremely rare. In the present study, we describe a family with segregation of c.-31G>T TPO mutation in the 5' UTR region in four subjects with thrombocythemia. Three of these patients also present congenital transverse limb defects. Association of these events gives a strong hint of the in vivo involvement of thrombopoietin in vasculogenesis, confirming the role of TPO in human development of the hemangioblast, the embryonic progenitor of the hematopoietic and endothelial lineages. This is the first report showing that vascular disruptions could be secondary to specific gene derangements.
