Herein, we report a novel pathogenic variant responsible for CAMT and provide new insights into the mechanisms regulating the transcription of the THPO gene.Ĭongenital amegakaryocytic thrombocytopenia caused by deleterious homozygous or compound heterozygous mutations in MPL (CAMT-MPL) is a rare inherited bone marrow failure syndrome presenting as an isolated thrombocytopenia at birth progressing to pancytopenia due to exhaustion of hematopoietic progenitors. Based on these findings, the patient was treated with the THPOmimetic agent eltrombopag, inducing a significant increase in platelet count and stable remission of bleeding symptoms. Accordingly, in the proband the serum THPO concentration indicates defective THPO production. Though mechanisms controlling the THPO transcription are not characterized, bioinformatics and in vitro analysis showed that c.-323C>T prevents the binding of transcription factors ETS1 and STAT4 to the putative THPO promoter, impairing THPO expression.
In a child with CAMT clinical picture, we identified the homozygous c.-323C>T substitution, affecting a potential regulatory region of THPO. CAMT can be also due to mutations affecting the THPO coding region (CAMT-THPO). CAMT is mostly caused by mutations in MPL (CAMT-MPL), the gene encoding the receptor of thrombopoietin (THPO), a crucial cytokine regulating hematopoiesis. Congenital amegakaryocytic thrombocytopenia (CAMT) is a recessive disorder characterized by severe reduction of megakaryocytes and platelets at birth, which evolves toward bone marrow aplasia in childhood.
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