• 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, and Alessandro Pecci.
• Medical Genetics, Department of Reproductive and Developmental Sciences, IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy. savoia@burlo.trieste.it
• Thromb. Haemost. 2010 Apr 1; 103 (4): 826-32.

AbstractMYH9-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.

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