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Your search keyword '"Malattia MYH9 associata"' showing total 3 results
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3 results on '"Malattia MYH9 associata"'

1. MYH9related disease: A novel missense Ala95Asp mutation of theMYH9gene

Author

Alessandro Pecci, Giorgia Girotto, Daniela De Rocco, Paula G. Heller, Annalisa Pastore, Ana C. Glembotsky, Felisa C. Molinas, Rosana F. Marta, Anna Savoia, Valeria Bozzi, DE ROCCO, Daniela, Heller, Pg, Girotto, Giorgia, Pastore, A, Glembotsky, Ac, Marta, Rf, Bozzi, V, Pecci, A, Molinas, Fc, Savoia, Anna, de Rocco, D., Heller, P. G., Girotto, G., Pastore, Annalisa, Glembotsky, A. C., Marta, R. F., Bozzi, V., Pecci, Alessandro, Molinas, F. C., and Savoia, A.

Subjects
Adult, Male, Models, Molecular, CIENCIAS MÉDICAS Y DE LA SALUD, neutrophil aggregate, DNA Mutational Analysis, Molecular Sequence Data, MYH9 gene, Mutation, Missense, Disease, MYH9-related disease, Malattia MYH9 associata, Biology, Inclusion bodies, mutational screening, Myosin, macrothrombocytopenia, medicine, Animals, Humans, Missense mutation, Amino Acid Sequence, Gene, Genetics, Aspartic Acid, Alanine, Base Sequence, Myosin Heavy Chains, Molecular Motor Proteins, Hematology, General Medicine, Bioquímica y Biología Molecular, medicine.disease, Pedigree, Protein Structure, Tertiary, Medicina Básica, Mutation (genetic algorithm), Immunology, Female, Sequence Alignment, Nephritis, Kidney disease
Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA. Patients present with congenital macrothrombocytopenia and inclusion bodies in neutrophils and might develop sensorineural deafness, presenile cataract, and/or progressive nephritis leading to end-stage renal failure. In a family with eight individuals suffering from macrothrombocytopenia and hearing impairment we identified a novel c.Ala95Asp mutation. Affecting the motor domain of the protein, the mutation is likely to be associated with a severe phenotype. Therefore, this family should be carefully monitored to follow-up the renal status even though the affected members do not seem to be at risk of early kidney disease. Fil: de Rocco, Daniela. Università degli Studi di Trieste; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Girotto, Giorgia. Università degli Studi di Trieste; Italia Fil: Pastore, Annalisa. National Institute for Medical Research; Reino Unido Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Bozzi, Valeria. Universita Degli Studi Di Pavia; Italia Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia Fil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Savoia, Anna. Università degli Studi di Trieste; Italia

Published
2009
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2. Megakaryocyte and platelet abnormalities in a patient with a W33C mutation in the conserved SH3-like domain of myosin heavy chain IIA

Author

Sheila Butchart, Ling Li, Chanchai Traivaree, Julie D. Forman-Kay, Elliott J. Stollar, Hilary Christensen, Fred G. Pluthero, Victor S. Blanchette, Daniela De Rocco, Walter H. A. Kahr, Anna Savoia, Julie Curtin, Kahr, Wh, Savoia, Anna, Pluthero, Fg, Li, L, Christensen, H, DE ROCCO, Daniela, Traivaree, C, Butchart, Se, Curtin, J, Stollar, Ej, Forman Kay, Jd, and Blanchette, V. S.

Subjects
Blood Platelets, Male, Models, Molecular, Heterozygote, MYH9-related disorder: megakaryocytes, Mutation, Missense, Biology, Malattia MYH9 associata, Immunoglobulin light chain, medicine.disease_cause, myosin IIA, Inclusion bodies, src Homology Domains, chemistry.chemical_compound, Megakaryocyte, Microscopy, Electron, Transmission, Myosin, medicine, Missense mutation, Inherited macrothrombocytopenia, Humans, Platelet, Child, emperipolesis, Conserved Sequence, Inclusion Bodies, Mutation, Myosin Heavy Chains, Molecular Motor Proteins, Hematology, Molecular biology, Thrombocytopenia, Adenosine diphosphate, medicine.anatomical_structure, chemistry, Biochemistry, Amino Acid Substitution, Case-Control Studies, Female, Blood Platelet Disorders, Megakaryocytes, Granulocytes
Abstract

SummaryHeterozygous mutations in MYH9, which encodes non-muscle myosin heavy chain IIA (MHC-IIA),result in autosomal dominant inherited MYH9-related disorders characterised by macrothrombocytopenia, granulocyte inclusions, variable sensorineural deafness, cataracts and nephritis. MHC-IIA is assembled into a complex consisting of two pairs of light chains and two heavy chains, where the latter contain a neck region, SH3-like, motor and rod domains. We describe a patient with a Trp33Cys missense mutation in the SH3-like domain of MHC-IIA. Abnormal platelet function was observed using platelet aggregometry with the agonists epinephrine and adenosine diphosphate (ADP). Patient granulocytes and megakaryocytes, but not platelets, contained abnormal MHC-IIA inclusions visualised by confocal immunofluorescence or electron microscopy. Megakaryocytes grown in culture were smaller and contained hypolobulated nuclei compared to controls. Bone marrow-derived megakaryocytes revealed a preponderance of immature forms, the presence of structurally diverse inclusion bodies, and frequent emperipolesis as assessed by electron microscopy. Platelets and leukocytes contained indistinguishable amounts of total MHCIIA determined by immunoblotting. Molecular modelling studies indicated that mutation of Trp33 destabilises the interface between the SH3-like and motor domain of MHC-IIA, which is close to previously described motor domain mutations, implying an important structural and/or functional role for this region in MHC-IIA.

Published
2009

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

Author

Paula G. Heller, Andrew D Mumford, Fabrizio Fabris, Alessandro Pecci, Silvia Riondino, Marco R. de Groot, Daniela De Rocco, Marisa Giani, Nuria Pujol-Moix, Francesca Scognamiglio, Valeria Bozzi, Marco Seri, Giuseppe Loffredo, Patrizia Noris, Anna Savoia, Raffaella Scandellari, Emanuele Panza, Carlo L. Balduini, Paolo Freddi, Savoia A., De Rocco D., Panza E., Bozzi V., Scandellari R., Loffredo G., Mumford A., Heller P.G., Noris P., De Groot M.R., Giani M., Freddi P., Scognamiglio F., Riondino S., Pujol-Moix N., Fabris F., Seri M., Balduini C.L., Pecci A., Savoia, Anna, DE ROCCO, Daniela, Panza, E, Bozzi, V, Scandellari, R, Loffredo, G, Mumford, A, Heller, Pg, Noris, P, DE GROOT, Mr, Giani, M, Freddi, P, Scognamiglio, F, Riondino, S, PUJOL MOIX, N, Fabris, F, Seri, M, Balduini, Cl, and Pecci, A.

Subjects
Male, Pathology, Cytoplasmic inclusion, Neutrophils, inclusioni in neutrofili, Mutant, DNA Mutational Analysis, piastrinopenia, Fluorescent Antibody Technique, Medicina Clínica, medicine.disease_cause, MYH9-related diseases, malattia MYH9 associata, Immunopathology, Myosin, Prospective Studies, Registries, Child, gene MYH9, Aged, 80 and over, Inclusion Bodies, Mutation, medicine.diagnostic_test, Molecular Motor Proteins, Hematology, Middle Aged, Italy, Child, Preschool, Sensorineural hearing loss, Female, Adult, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Adolescent, Giant platelets, MYH9 gene, Biology, Immunofluorescence, Sensitivity and Specificity, Young Adult, Predictive Value of Tests, medicine, Humans, Hematología, Aged, Myosin Heavy Chains, medicine.disease, Thrombocytopenia, Heavy chain disease, Microscopy, Fluorescence, Case-Control Studies, Neutrophil inclusions
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. Fil: Savoia, Anna. Universita Degli Studi Di Trieste; Italia. Italian Registry for MYH9-Related Disease; Italia Fil: de Rocco, Daniela. Universita Degli Studi Di Trieste; Italia. Italian Registry for MYH9-Related Disease; Italia Fil: Panza, Emanuele. Italian Registry for MYH9-Related Disease; Italia. Universita Di Bologna; Italia Fil: Bozzi, Valeria. Italian Registry for MYH9-Related Disease; Italia. University of Pavia; Italia Fil: Scandellari, Raffaella. Italian Registry for MYH9-Related Disease; Italia. Universita Di Padova; Italia Fil: Loffredo, Giuseppe. Italian Registry for MYH9-Related Disease; Italia. Pausilipon Hospital; Italia Fil: Mumford, Andrew. University of Bristol; Reino Unido Fil: Heller, Paula Graciela. Italian Registry for MYH9-Related Disease; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Noris, Patrizia. Italian Registry for MYH9-Related Disease; Italia Fil: de Groot, Marco R.. University of Bristol; Reino Unido Fil: Giani, Marisa. Italian Registry for MYH9-Related Disease; Italia. Istituto di Ricovero e Cura a Carattere Scientifico; Italia Fil: Freddi, Paolo. Italian Registry for MYH9-Related Disease; Italia Fil: Scognamiglio, Francesca. Italian Registry for MYH9-Related Disease; Italia Fil: Riondino, Silvia. Italian Registry for MYH9-Related Disease; Italia. Istituto di Ricovero e Cura a Carattere Scientifico; Italia Fil: Pujol Moix, Núria. Universitat Autonoma de Barcelona; España Fil: Fabris, Fabrizio. Italian Registry for MYH9-Related Disease; Italia. Universita Di Padova; Italia Fil: Seri, Marco. Italian Registry for MYH9-Related Disease; Italia. Universita Di Bologna; Italia Fil: Balduini, Carlo L.. Italian Registry for MYH9-Related Disease; Italia. University of Pavia; Italia Fil: Pecci, Alessandro. Italian Registry for MYH9-Related Disease; Italia. University of Pavia; Italia

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