Heavy chain myosin 9-related disease (MYH9-RD): Neutrophil inclusions of myosin-9 as a pathognomonic sign of the disorder

Anna Savoia, Daniela De Rocco, Emanuele Panza, Valeria Bozzi, Raffaella Scandellari, Giuseppe Loffredo, Andrew Mumford, Paula G. Heller, Patrizia Noris, Marco R. De Groot, Marisa Giani, Paolo Freddi, Francesca Scognamiglio, Silvia Riondino, Núria Pujol-Moix, Fabrizio Fabris, Marco Seri, Carlo L. Balduini, Alessandro Pecci

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MYH9-related disease (MYH9-RD) is an autosomal dominant thrombocytopenia with giant platelets variably associated with young-adult onset of progressive sensorineural hearing loss, presenile cataract, and renal damage. MYH9-RD is caused by mutations of MYH9, the gene encoding for non-muscle heavy-chain myosin-9. Wild-type and mutant myosin-9 aggregate as cytoplasmic inclusions in patients' leukocytes, the identification of which by immunofluorescence has been proposed as a suitable tool for the diagnosis of MYH9-RD. Since the predictive value of this assay, in terms of sensitivity and specificity, is unknown, we investigated 118 consecutive unrelated patients with a clinical presentation strongly consistent with MYH9-RD. All patients prospectively underwent both the immunofluorescence assay for myosin-9 aggregate detection and molecular genetic analysis of the MYH9 gene. Myosin-9 aggregates were identified in 82 patients, 80 of which (98%) had also a MYH9 mutation. In the remaining 36 patients neither myosin-9 aggregates nor MYH9 mutations were found. Sensitivity and specificity of the immunofluorescence assay was evaluated to be 100% and 95%, respectively. Except for the presence of aggregates, we did not find any other significant difference between patients with or without aggregates, demonstrating that the myosin-9 inclusions in neutrophils are a pathognomonic sign of the disease. However, the identification of the specific MYH9 mutation is still of importance for prognostic aspects of MYH9-RD. © Schattauer 2010.
Original languageEnglish
Pages (from-to)826-832
JournalThrombosis and Haemostasis
Issue number4
Publication statusPublished - 1 Apr 2010


  • Giant platelets
  • MYH9 gene
  • MYH9-related diseases
  • Neutrophil inclusions
  • Thrombocytopenia


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