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

SAVOIA ANNA; DE ROCCO D; PANZA EMANUELE; BOZZI V; SCANDELLARI R; LOFFREDO G; MUMFORD A; HELLER PAULA G; NORIS PATRICIA; DE GROOT MR; GIANI M; FREDDI P; SCOGNAMIGLIO F; RIONDINO S; PUJOL-MOIX N; FABRIS F; SERI M; BALDUINI CL; PECCI ALESSANDRO

THROMBOSIS AND HAEMOSTASIS

SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN

Lugar: Stuttgart, Alemania; Año: 2010 vol. 103 p. 826 - 832

0340-6245

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.