title: Heavy chain myosin 9-related disease (MYH9 -RD): neutrophil inclusions of myosin-9 as a pathognomonic sign of the disorder.
abstract: 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.
authors.affiliation: Medical Genetics, Department of Reproductive and Developmental Sciences, IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy. savoia@burlo.trieste.it
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.forename: Emanuele
authors.initials: E
authors.lastname: Panza
authors.forename: Valeria
authors.initials: V
authors.lastname: Bozzi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scandellari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Loffredo
authors.forename: Andrew
authors.initials: A
authors.lastname: Mumford
authors.forename: Paula G
authors.initials: PG
authors.lastname: Heller
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Marco R
authors.initials: MR
authors.lastname: De Groot
authors.forename: Marisa
authors.initials: M
authors.lastname: Giani
authors.forename: Paolo
authors.initials: P
authors.lastname: Freddi
authors.forename: Francesca
authors.initials: F
authors.lastname: Scognamiglio
authors.forename: Silvia
authors.initials: S
authors.lastname: Riondino
authors.forename: Núria
authors.initials: N
authors.lastname: Pujol-Moix
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fabris
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D007558:Italy; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000097:blood* / Q000235:genetics; D009154:Mutation; D018995:Myosin Heavy Chains / Q000097:blood* / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012042:Registries; D012680:Sensitivity and Specificity; D013921:Thrombocytopenia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains