Thrombocytopenia resulting from mutations in filamin A can be expressed as an isolated syndrome

Blood. 2011 Nov 24;118(22):5928-37. doi: 10.1182/blood-2011-07-365601. Epub 2011 Sep 29.


Filaminopathies A caused by mutations in the X-linked FLNA gene are responsible for a wide spectrum of rare diseases including 2 main phenotypes, the X-linked dominant form of periventricular nodular heterotopia (FLNA-PVNH) and the otopalatodigital syndrome spectrum of disorders. In platelets, filamin A (FLNa) tethers the principal receptors ensuring the platelet-vessel wall interaction, glycoprotein Ibα and integrin αIIbβ3, to the underlying cytoskeleton. Hemorrhage, coagulopathy, and thrombocytopenia are mentioned in several reports on patients with FLNA-PVNH. Abnormal platelet morphology in 2 patients with FLNA-PVNH prompted us to examine a third patient with similar platelet morphology previously diagnosed with immunologic thrombocytopenic purpura. Her enlarged platelets showed signs of FLNa degradation in Western blotting, and a heterozygous missense mutation in FLNA was detected. An irregular distribution of FLNa within the total platelet population was shown by confocal microscopy for all 3 patients. In vitro megakaryocyte cultures showed an abnormal differentiation, including an irregular distribution of FLNa with a frayed aspect, the presence of enlarged α-granules, and an abnormal fragmentation of the cytoplasm. Mutations in FLNA may represent an unrecognized cause of macrothrombocytopenia with an altered platelet production and a modified platelet-vessel wall interaction.

Publication types

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

MeSH terms

  • Aged
  • Cells, Cultured
  • Contractile Proteins / genetics*
  • Female
  • Filamins
  • Genetic Predisposition to Disease
  • Humans
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Mutation* / physiology
  • Platelet Count
  • Syndrome
  • Thrombocytopenia / blood
  • Thrombocytopenia / classification*
  • Thrombocytopenia / diagnosis
  • Thrombocytopenia / genetics*


  • Contractile Proteins
  • Filamins
  • Microfilament Proteins