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.
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.
In addition to the clinical importance of recognizing this disorder, characterization of mutations identified in patients with CAMT has led to insights into thrombopoietin receptor structure and function.
Recently, we and others could define the molecular cause of the rare disease congenital amegakaryocytic thrombocytopenia (CAMT) as mutations in the c-mpl gene (Blood 97: 139, 2001).
We describe a CAMT patient with compound heterozygous mutations of the causative MPL gene (one being a previously unreported splice site mutation in intron 11) who developed pancytopenia within the first month of life.
Because the c-mpl gene was considered as one of the candidate genes for this disorder, we analyzed the genomic sequence of the c-mpl gene of a 10-year-old Japanese girl with CAMT.
Here, we report for the first time two different MPL amino-acid substitutions in a 2-year-old Italian boy with CAMT and compound heterozygosis for two (c-mpl point mutations.
Germline loss-of-function (LOF) JAK3 and MPL mutations cause severe combined immunodeficiency and congenital amegakaryocytic thrombocytopenia, respectively.
F104S c-Mpl responds to a transmembrane domain-binding thrombopoietin receptor agonist: proof of concept that selected receptor mutations in congenital amegakaryocytic thrombocytopenia can be stimulated with alternative thrombopoietic agents.