Inherited thrombocytopenias: toward a molecular understanding of disorders of platelet production.
OBJECTIVE
To review the defined syndromes of inherited thrombocytopenia and discuss new genetic data for several disorders that shed light on the process of megakaryopoiesis.


RESULTS
The genes responsible for several inherited thrombocytopenias have been recently discovered, including congenital amegakaryocytic leukemia, amegakaryocytic thrombocytopenia with radio-ulnar synostosis, familial platelet syndrome with predisposition to acute myelogenous leukemia, Paris-Trousseau, Wiskott-Aldrich syndrome, and the May-Hegglin, Sebastian, Epstein, and Fechner syndromes. These clinical syndromes, combined with studies in mouse and in vitro models, reveal the importance of these genes for normal hematopoiesis.


CONCLUSIONS
Although inherited syndromes of thrombocytopenia are rare, characterization of mutations in these disorders has contributed greatly to our understanding of megakaryocyte and platelet development. A systematic registry of congenitally thrombocytopenic individuals would almost certainly lead to new genetic discoveries.
Geddis
Amy E
AE
Department of Pediatrics, University of California, San Diego, USA. Ageddis@ucsd.edu
Kaushansky
Kenneth
K
D000818:Animals; D001791:Blood Platelet Disorders / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology; D034061:Thrombopoiesis / Q000235:genetics
D004268:DNA-Binding Proteins; C484298:HOXA11 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C069634:HOXA10 protein, human