Thrombocytopenia 12 with or without myopathy

An inherited thrombocytopenia caused by a variation in the GNE gene, characterized by reduced platelet count, enlarged platelets, and a bleeding tendency, with onset in childhood or early adulthood. Clinical studies describe abnormal megakaryocyte maturation and a defect in platelet surface sialylation, resulting from impaired activity of the bifunctional GNE enzyme responsible for the initial steps of sialic-acid biosynthesis. Additional work in patient-derived cells shows altered GNE protein expression and reduced surface sialylation, leading to defective proplatelet formation and shortened platelet survival.