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

Anna Savoia
1  Medical Genetics, Department of Reproductive and Developmental Sciences, Institute for Maternal and Child Health – IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Daniela De Rocco
1  Medical Genetics, Department of Reproductive and Developmental Sciences, Institute for Maternal and Child Health – IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Emanuele Panza
2  Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Valeria Bozzi
3  Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Raffaella Scandellari
4  Department of Medical Sciences, University of Padova, Padova, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Giuseppe Loffredo
5  Department of Oncology, Azienda „Santobono-Pausilipon“, Pausilipon Hospital, Napoli, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Andrew Mumford
6  Bristol Heart Institute, University of Bristol, Bristol, UK
,
Paula G. Heller
7  Instituto de Investigaciones Medicas (IDIM), “A. Lanari”, University of Buenos Aires, Buenos Aires, Argentina
,
Patrizia Noris
3  Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Marco R. De Groot
8  Department of Internal Medicine, Medical Spectrum Twente, Enschede, The Netherlands
,
Marisa Giani
9  Pediatric Nephrology Unit, IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Paolo Freddi
10  Nephrology Unit, Ospedali Riuniti, Ancona, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Francesca Scognamiglio
11  Hematology Unit, “San Bortolo” Hospital, Vicenza, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Silvia Riondino
12  Department of Laboratory Medicine & Advanced Technologies, IRCCS San Raffaele Pisana, Rome, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Núria Pujol-Moix
13  Autonomous University of Barcelona & Platelet Pathology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Fabrizio Fabris
4  Department of Medical Sciences, University of Padova, Padova, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Marco Seri
2  Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Carlo L. Balduini
3  Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
,
Alessandro Pecci
3  Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
14  Italian Registry for MYH9-Related Disease, Pavia, Italy
› Author Affiliations
Further Information

Publication History

Received: 26 August 2009

Accepted after minor revision: 06 February 2009

Publication Date:
22 November 2017 (online)

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.