thrombocytopenia 2

MONDO:0008555

An autosomal dominant thrombocytopenia caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability, mild to moderate reductions in platelet count, platelets that are generally normal in size, and a mild mucocutaneous bleeding tendency. Individuals show normal platelet ultrastructure and typically have no associated syndromic abnormalities, but megakaryocyte maturation is abnormal, reflecting dysregulated thrombopoiesis. Pathogenic variants occur exclusively in the 5' untranslated region (5'UTR) of ANKRD26, and variants cause gain-of-function overexpression during megakaryopoiesis, disrupting normal signaling and impairing proplatelet formation.