MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease.
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure syndrome. Mutations in the gene for the thrombopoietin receptor MPL were defined as the molecular cause in CAMT patients. Extending our sequence analyses from eight to a total of now 23 CAMT patients we could verify our hypothesis of genotype-phenotype correlation in CAMT. Seven different mutations predicted to lead to a complete loss of function of the thrombopoietin receptor were found in 13 patients belonging to group CAMT I with persistently low platelet counts and a fast progression into pancytopenia. Nine different missense mutations were detected in 10 patients of group CAMT II, characterized by a transient increase in platelet counts over 50 nl(-1) during the first years of life. 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.
Germeshausen
Manuela
M
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany. Germeshausen.Manuela@mh-hannover.de
Ballmaier
Matthias
M
Welte
Karl
K
D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D002648:Child; D002675:Child, Preschool; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007223:Infant; D008533:Megakaryocytes / Q000166:cytology*; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D018121:Receptors, Cytokine / Q000235:genetics* / Q000502:physiology; D053628:Receptors, Thrombopoietin; D017386:Sequence Homology, Amino Acid; D013921:Thrombocytopenia / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human