title: Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation.
abstract: 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 G185T TPO mutation in the 5' UTR region in 4 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.
authors: Unitá Operativa Genetica Medica, Policlinico Sant'Orsola-Malpighi, Dipartimento di Scienze Ginecologiche, Ostetriche Pediatriche Università degli Studi di Bologna, Bologna, Italy. claudio.graziano@unibo.it
authors: Claudio
authors: C
authors: Graziano
authors: Simona
authors: S
authors: Carone
authors: Emanuele
authors: E
authors: Panza
authors: Flora
authors: F
authors: Marino
authors: Pamela
authors: P
authors: Magini
authors: Giovanni
authors: G
authors: Romeo
authors: Andrea
authors: A
authors: Pession
authors: Marco
authors: M
authors: Seri
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000150:complications* / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011247:Pregnancy; D013922:Thrombocytosis / Q000150:complications* / Q000235:genetics*; D013926:Thrombopoietin / Q000235:genetics*
chemical_list: D013926:Thrombopoietin