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

doi:10.1160/TH09-08-0593

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2010; 103(04): 826-832
DOI: 10.1160/TH09-08-0593

New Technologies, Dignostic Tools and Drugs

Schattauer GmbH

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

Autor*innen

Anna Savoia

¹Medical Genetics, Department of Reproductive and Developmental Sciences, Institute for Maternal and Child Health – IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Daniela De Rocco

¹Medical Genetics, Department of Reproductive and Developmental Sciences, Institute for Maternal and Child Health – IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Emanuele Panza

²Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Valeria Bozzi

³Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Raffaella Scandellari

⁴Department of Medical Sciences, University of Padova, Padova, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Giuseppe Loffredo

⁵Department of Oncology, Azienda „Santobono-Pausilipon“, Pausilipon Hospital, Napoli, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Andrew Mumford

⁶Bristol Heart Institute, University of Bristol, Bristol, UK
Paula G. Heller

⁷Instituto de Investigaciones Medicas (IDIM), “A. Lanari”, University of Buenos Aires, Buenos Aires, Argentina
Patrizia Noris

³Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Marco R. De Groot

⁸Department of Internal Medicine, Medical Spectrum Twente, Enschede, The Netherlands
Marisa Giani

⁹Pediatric Nephrology Unit, IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Paolo Freddi

¹⁰Nephrology Unit, Ospedali Riuniti, Ancona, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Francesca Scognamiglio

¹¹Hematology Unit, “San Bortolo” Hospital, Vicenza, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Silvia Riondino

¹²Department of Laboratory Medicine & Advanced Technologies, IRCCS San Raffaele Pisana, Rome, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Núria Pujol-Moix

¹³Autonomous University of Barcelona & Platelet Pathology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Fabrizio Fabris

⁴Department of Medical Sciences, University of Padova, Padova, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Marco Seri

²Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Carlo L. Balduini

³Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy
Alessandro Pecci

³Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy

¹⁴Italian Registry for MYH9-Related Disease, Pavia, Italy

Abstract

Summary

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.

Keywords

MYH9-related diseases - thrombocytopenia - giant platelets - MYH9 gene - neutrophil inclusions

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Referenzen

References
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