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

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 heav...

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Detalhes bibliográficos
Autores: Savoia, Anna, de Rocco, Daniela, Panza, Emanuele, Bozzi, Valeria, Scandellari, Raffaella, Loffredo, Giuseppe, Mumford, Andrew, Heller, Paula Graciela, Noris, Patrizia, de Groot, Marco R., Giani, Marisa, Freddi, Paolo, Scognamiglio, Francesca, Riondino, Silvia, Pujol Moix, Núria, Fabris, Fabrizio, Seri, Marco, Balduini, Carlo L., Pecci, Alessandro
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/15532
Acesso em linha:http://hdl.handle.net/11336/15532
Access Level:acceso abierto
Palavra-chave:Myh9-Related Diseases
Thrombocytopenia
Giant Platelets
Myh9 Gene
Neutrophil Inclusions
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Descrição
Resumo: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.

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