Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease
- Autores
- Pecci, Alessandro; Panza, Emanuele; Pujol Moix, Núria; Klersy, Catherine; Di Bari, Filomena; Bozzi, Valeria; Gresele, Paolo; Lethagen, Stefan; Fabris, Fabrizio; Dufour, Carlo; Granata, Antonio; Doubek, Michael; Pecoraro, Carmine; Koivisto, Pasi A.; Heller, Paula Graciela; Iolascon, Achille; Alvisi, Patrizia; Schwabe, Dirk; De Candia, Erica; Rocca, Bianca; Russo, Umberto; Ramenghi, Ugo; Noris, Patrizia; Seri, Marco; Balduini, Carlo L.; Savoia, Anna
- Año de publicación
- 2008
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease.We have evaluated 108 consecutive MYH9- RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis.We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9-RD cases).We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients’ clinical management but also to the elucidation of the pathogenesis of the disease.
Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Panza, Emanuele. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Universidad de Bologna; Italia
Fil: Pujol Moix, Núria. Hospital de la Santa Creu i Sant Pau; España
Fil: Klersy, Catherine. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Di Bari, Filomena. Telethon Institute of Genetics and Medicine; Italia
Fil: Bozzi, Valeria. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Gresele, Paolo. Università di Perugia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Lethagen, Stefan. Universidad de Copenhagen; Dinamarca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Fabris, Fabrizio. Università di Padova; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Dufour, Carlo. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Granata, Antonio. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Policlinico "Vittorio Emanuele"; Italia
Fil: Doubek, Michael. University Hospital; República Checa
Fil: Pecoraro, Carmine. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. ‘‘Santobono’’ Children’s Hospital; Italia
Fil: Koivisto, Pasi A.. Tampere University Hospital; Finlandia
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: Iolascon, Achille. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli Studi di Napoli Federico II; Italia
Fil: Alvisi, Patrizia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Ospedale Maggiore Carlo Alberto Pizzardi; Italia
Fil: Schwabe, Dirk. Goethe Universitat Frankfurt; Alemania
Fil: De Candia, Erica. Università degli studi di Roma "La Sapienza"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Rocca, Bianca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli studi di Roma "La Sapienza"; Italia
Fil: Russo, Umberto. Ospedale Luigi Sacco; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Ramenghi, Ugo. Università degli studi di Torino; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia
Fil: Seri, Marco. Universidad de Bologna; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia
Fil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia
Fil: Savoia, Anna. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia - Materia
-
MYH9 GENE
INHERITED THROMBOCYTOPENIA
MYH9-RELATED DISEASE
MUTATION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/105263
Ver los metadatos del registro completo
| id |
CONICETDig_97b97739e5bbbe4189ae4d2ba314aa39 |
|---|---|
| oai_identifier_str |
oai:ri.conicet.gov.ar:11336/105263 |
| network_acronym_str |
CONICETDig |
| repository_id_str |
3498 |
| network_name_str |
CONICET Digital (CONICET) |
| spelling |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related diseasePecci, AlessandroPanza, EmanuelePujol Moix, NúriaKlersy, CatherineDi Bari, FilomenaBozzi, ValeriaGresele, PaoloLethagen, StefanFabris, FabrizioDufour, CarloGranata, AntonioDoubek, MichaelPecoraro, CarmineKoivisto, Pasi A.Heller, Paula GracielaIolascon, AchilleAlvisi, PatriziaSchwabe, DirkDe Candia, EricaRocca, BiancaRusso, UmbertoRamenghi, UgoNoris, PatriziaSeri, MarcoBalduini, Carlo L.Savoia, AnnaMYH9 GENEINHERITED THROMBOCYTOPENIAMYH9-RELATED DISEASEMUTATIONhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease.We have evaluated 108 consecutive MYH9- RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis.We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9-RD cases).We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients’ clinical management but also to the elucidation of the pathogenesis of the disease.Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Panza, Emanuele. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Universidad de Bologna; ItaliaFil: Pujol Moix, Núria. Hospital de la Santa Creu i Sant Pau; EspañaFil: Klersy, Catherine. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Di Bari, Filomena. Telethon Institute of Genetics and Medicine; ItaliaFil: Bozzi, Valeria. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Gresele, Paolo. Università di Perugia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Lethagen, Stefan. Universidad de Copenhagen; Dinamarca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Fabris, Fabrizio. Università di Padova; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Dufour, Carlo. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Granata, Antonio. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Policlinico "Vittorio Emanuele"; ItaliaFil: Doubek, Michael. University Hospital; República ChecaFil: Pecoraro, Carmine. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. ‘‘Santobono’’ Children’s Hospital; ItaliaFil: Koivisto, Pasi A.. Tampere University Hospital; FinlandiaFil: 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; ArgentinaFil: Iolascon, Achille. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli Studi di Napoli Federico II; ItaliaFil: Alvisi, Patrizia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Ospedale Maggiore Carlo Alberto Pizzardi; ItaliaFil: Schwabe, Dirk. Goethe Universitat Frankfurt; AlemaniaFil: De Candia, Erica. Università degli studi di Roma "La Sapienza"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Rocca, Bianca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli studi di Roma "La Sapienza"; ItaliaFil: Russo, Umberto. Ospedale Luigi Sacco; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Ramenghi, Ugo. Università degli studi di Torino; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; ItaliaFil: Seri, Marco. Universidad de Bologna; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaFil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; ItaliaFil: Savoia, Anna. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; ItaliaWiley-liss, Div John Wiley & Sons Inc2008-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105263Pecci, Alessandro; Panza, Emanuele; Pujol Moix, Núria; Klersy, Catherine; Di Bari, Filomena; et al.; Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 29; 3; 3-2008; 409-4171059-7794CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.20661info:eu-repo/semantics/altIdentifier/doi/10.1002/humu.20661info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:16:21Zoai:ri.conicet.gov.ar:11336/105263instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:16:21.925CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| title |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| spellingShingle |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease Pecci, Alessandro MYH9 GENE INHERITED THROMBOCYTOPENIA MYH9-RELATED DISEASE MUTATION |
| title_short |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| title_full |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| title_fullStr |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| title_full_unstemmed |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| title_sort |
Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease |
| dc.creator.none.fl_str_mv |
Pecci, Alessandro Panza, Emanuele Pujol Moix, Núria Klersy, Catherine Di Bari, Filomena Bozzi, Valeria Gresele, Paolo Lethagen, Stefan Fabris, Fabrizio Dufour, Carlo Granata, Antonio Doubek, Michael Pecoraro, Carmine Koivisto, Pasi A. Heller, Paula Graciela Iolascon, Achille Alvisi, Patrizia Schwabe, Dirk De Candia, Erica Rocca, Bianca Russo, Umberto Ramenghi, Ugo Noris, Patrizia Seri, Marco Balduini, Carlo L. Savoia, Anna |
| author |
Pecci, Alessandro |
| author_facet |
Pecci, Alessandro Panza, Emanuele Pujol Moix, Núria Klersy, Catherine Di Bari, Filomena Bozzi, Valeria Gresele, Paolo Lethagen, Stefan Fabris, Fabrizio Dufour, Carlo Granata, Antonio Doubek, Michael Pecoraro, Carmine Koivisto, Pasi A. Heller, Paula Graciela Iolascon, Achille Alvisi, Patrizia Schwabe, Dirk De Candia, Erica Rocca, Bianca Russo, Umberto Ramenghi, Ugo Noris, Patrizia Seri, Marco Balduini, Carlo L. Savoia, Anna |
| author_role |
author |
| author2 |
Panza, Emanuele Pujol Moix, Núria Klersy, Catherine Di Bari, Filomena Bozzi, Valeria Gresele, Paolo Lethagen, Stefan Fabris, Fabrizio Dufour, Carlo Granata, Antonio Doubek, Michael Pecoraro, Carmine Koivisto, Pasi A. Heller, Paula Graciela Iolascon, Achille Alvisi, Patrizia Schwabe, Dirk De Candia, Erica Rocca, Bianca Russo, Umberto Ramenghi, Ugo Noris, Patrizia Seri, Marco Balduini, Carlo L. Savoia, Anna |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
MYH9 GENE INHERITED THROMBOCYTOPENIA MYH9-RELATED DISEASE MUTATION |
| topic |
MYH9 GENE INHERITED THROMBOCYTOPENIA MYH9-RELATED DISEASE MUTATION |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease.We have evaluated 108 consecutive MYH9- RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis.We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9-RD cases).We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients’ clinical management but also to the elucidation of the pathogenesis of the disease. Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Panza, Emanuele. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Universidad de Bologna; Italia Fil: Pujol Moix, Núria. Hospital de la Santa Creu i Sant Pau; España Fil: Klersy, Catherine. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Di Bari, Filomena. Telethon Institute of Genetics and Medicine; Italia Fil: Bozzi, Valeria. Universita Degli Studi Di Pavia; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Gresele, Paolo. Università di Perugia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Lethagen, Stefan. Universidad de Copenhagen; Dinamarca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Fabris, Fabrizio. Università di Padova; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Dufour, Carlo. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Granata, Antonio. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Policlinico "Vittorio Emanuele"; Italia Fil: Doubek, Michael. University Hospital; República Checa Fil: Pecoraro, Carmine. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. ‘‘Santobono’’ Children’s Hospital; Italia Fil: Koivisto, Pasi A.. Tampere University Hospital; Finlandia 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: Iolascon, Achille. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli Studi di Napoli Federico II; Italia Fil: Alvisi, Patrizia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Ospedale Maggiore Carlo Alberto Pizzardi; Italia Fil: Schwabe, Dirk. Goethe Universitat Frankfurt; Alemania Fil: De Candia, Erica. Università degli studi di Roma "La Sapienza"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Rocca, Bianca. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Università degli studi di Roma "La Sapienza"; Italia Fil: Russo, Umberto. Ospedale Luigi Sacco; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Ramenghi, Ugo. Università degli studi di Torino; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia Fil: Seri, Marco. Universidad de Bologna; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia Fil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia Fil: Savoia, Anna. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia. IRCCS Policlinico San Matteo Foundation. Italian Registry for MYH9-Related Disease; Italia |
| description |
MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease.We have evaluated 108 consecutive MYH9- RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis.We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9-RD cases).We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients’ clinical management but also to the elucidation of the pathogenesis of the disease. |
| publishDate |
2008 |
| dc.date.none.fl_str_mv |
2008-03 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/105263 Pecci, Alessandro; Panza, Emanuele; Pujol Moix, Núria; Klersy, Catherine; Di Bari, Filomena; et al.; Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 29; 3; 3-2008; 409-417 1059-7794 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/105263 |
| identifier_str_mv |
Pecci, Alessandro; Panza, Emanuele; Pujol Moix, Núria; Klersy, Catherine; Di Bari, Filomena; et al.; Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history ofMYH9-related disease; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 29; 3; 3-2008; 409-417 1059-7794 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.20661 info:eu-repo/semantics/altIdentifier/doi/10.1002/humu.20661 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley-liss, Div John Wiley & Sons Inc |
| publisher.none.fl_str_mv |
Wiley-liss, Div John Wiley & Sons Inc |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1842980889216155648 |
| score |
12.993085 |