title: Defective expression of GPIb/IX/V complex in platelets from patients with May-Hegglin anomaly and Sebastian syndrome.
abstract: OBJECTIVE
  May-Hegglin anomaly (MHA) and Sebastian syndrome (SBS) are inherited macrothrombocytopenias with D hle-like bodies in leukocytes. MHA-SBS are due to mutations of the gene (MYH9) for the heavy chain of non-muscle myosin IIA (NMMHC-IIA), the only myosin II expressed in platelets. The bleeding tendency is often more severe than expected on the basis of platelet count, but no abnormality of platelet function has been identified. To characterize platelet abnormalities deriving from MYH9 mutations better, we studied surface glycoproteins (GPs) in platelets from MHA-SBS patients.
  
  
  METHODS
  Eight patients from 4 unrelated families were studied. Platelet surface GPs were studied by flow cytometry in both the whole platelet population and subpopulations of platelets identified according to their size.
  
  
  RESULTS
  Flow cytometry identified a defect of the GPIb/IX/V complex in the whole platelet population in 7 of 8 patients. Moreover, in all patients the subpopulation of large platelets had defective expression of this complex.
  
  
  CONCLUSIONS
  These findings indicate that MYH9 mutations may be responsible for reduced surface expression of GPIb/IX/V. This defect could contribute to the bleeding tendency of these patients. The identification of a GPIb/IX/V defect in MHA-SBS platelets raises the question of the differential diagnosis from heterozygous Bernard-Soulier syndrome.
authors.affiliation: Department of Internal Medicine, IRCCS S. Matteo Universit di Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Di Pumpo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Iride F
authors.initials: IF
authors.lastname: Ceresa
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
mesh_terms: D001791:Blood Platelet Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D020409:Molecular Motor Proteins / Q000235:genetics; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D013577:Syndrome; D013921:Thrombocytopenia / Q000378:metabolism* / Q000473:pathology
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains