Genetics of familial forms of thrombocytopenia

Hum Genet. 2012 Dec;131(12):1821-32. doi: 10.1007/s00439-012-1215-x. Epub 2012 Aug 11.


The joint application of clinical and genetic investigation to patients with inherited thrombocytopenias, as well as the availability of new methods for studying megakaryopoiesis, has greatly expanded the knowledge of these disorders in the last few years with regard to their etiology, pathogenesis and clinical aspects. In particular, new diseases have been described, as deriving from mutations in the genes FLNA, TUBB1, ITGA2/ITGB3, ANKRD26, CYCS, and ABCG5 or ABCG8. Moreover, forms previously considered separate entities were found to be different clinical aspects of a single disease. For instance, identification of MYH9 as the gene whose mutations cause the May-Hegglin anomaly led to the recognition that Sebastian platelet syndrome, Epstein syndrome, and Fechtner syndrome derive from mutations of the same gene and describe overlapping disorders. Despite these advances, knowledge of hereditary thrombocytopenias is still far from satisfactory because for approximately half of the patients it is not possible to formulate a definite diagnosis in that their illnesses has not yet been described. In this review, we provide a systematic description of hereditary thrombocytopenias as we know them today, giving special attention to genetic aspects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Ankyrin Repeat / genetics
  • Bernard-Soulier Syndrome / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Pair 11 / genetics
  • Congenital Bone Marrow Failure Syndromes
  • Contractile Proteins / genetics
  • Filamins
  • GATA1 Transcription Factor / genetics
  • Genetic Diseases, X-Linked / genetics
  • Gray Platelet Syndrome / genetics
  • Humans
  • Integrins / genetics
  • Jacobsen Distal 11q Deletion Syndrome / genetics
  • Microfilament Proteins / genetics
  • Molecular Motor Proteins / genetics
  • Mutation
  • Myosin Heavy Chains / genetics
  • Platelet Membrane Glycoproteins / genetics
  • Thrombocytopenia / blood
  • Thrombocytopenia / genetics*
  • Wiskott-Aldrich Syndrome / genetics
  • von Willebrand Diseases / genetics


  • ATP-Binding Cassette Transporters
  • Contractile Proteins
  • Filamins
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Integrins
  • MYH9 protein, human
  • Microfilament Proteins
  • Molecular Motor Proteins
  • Platelet Membrane Glycoproteins
  • Myosin Heavy Chains

Supplementary concepts

  • Chromosome 11q partial deletion
  • Congenital amegakaryocytic thrombocytopenia
  • Thrombocytopenia 1
  • Von Willebrand disease, platelet type