Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL).
Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia.
Mutations in the genes of hematopoietic growth factor receptors as a cause of congenital cytopenia, such as congenital amegakaryocytic thrombocytopenia (CAMT) or severe congenital neutropenia (CN), are discussed.
Previously, we identified an inherited syndrome of congenital amegakaryocytic thrombocytopenia and radio-ulnar synostosis that is associated with a point mutation in the third helix of HOXA11 homeodomain (HOXA11-DeltaH3).
We propose that a 21q22 deletion resulting in RUNX1 haploinsufficiency can produce a phenotype similar to CAMT with various associated anomalies depending on which adjacent genes are absent or disrupted.
Heterozygous mutations in <i>MECOM</i> (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis.
Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1.
Using in vitro assays with hematopoietic progenitors from patients of both patient groups we could provide experimental evidence for a residual activity of the thrombopoietin receptor in CAMT II patients.
Compound heterozygous c-Mpl mutations in a child with congenital amegakaryocytic thrombocytopenia: functional characterization and a review of the literature.
Using in vitro assays with hematopoietic progenitors from patients of both patient groups we could provide experimental evidence for a residual activity of the thrombopoietin receptor in CAMT II patients.
Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.