MYH9-Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype-Phenotype Correlations
| العنوان: | MYH9-Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype-Phenotype Correlations |
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| المؤلفون: | Pecci, A, Klersy, C, Gresele, P, Lee, K, De Rocco, D, Bozzi, V, Russo, G, Heller, Pg, Loffredo, G, Ballmaier, M, Fabris, F, Beggiato, E, Kahr, Wha, Pujol-Moix, N, Platokouki, H, Matthijs, G, Noris, P, Yerram, P, Hermans, C, Batzios, S, De Groot, M, Zieger, B, De Candia, E, Fraticelli, V, Kersseboom, R, Piccoli, Gb, Zimmermann, S, Zaninetti, C, Nicchia, E, Baronci, C, Seri, M, Knight, Pj, Balduini, Cl, Savoia, A, Van Geet, C, Geber, B, Economou, M, Fierro, T, Glembotsky, Ac, Vianello, F, Guthner, C. |
| المساهمون: | Pecci, A, Klersy, C, Gresele, P, Lee, Kj, De Rocco, D, Bozzi, V, Russo, G, Heller, Pg, Loffredo, G, Ballmaier, M, Fabris, F, Beggiato, E, Kahr, Wh, Pujol-Moix, N, Platokouki, H, Van Geet, C, Noris, P, Yerram, P, Hermans, C, Gerber, B, Economou, M, De Groot, M, Zieger, B, De Candia, E, Fraticelli, V, Kersseboom, R, Piccoli, Gb, Zimmermann, S, Fierro, T, Glembotsky, Ac, Vianello, F, Zaninetti, C, Nicchia, E, Güthner, C, Baronci, C, Seri, M, Knight, Pj, Balduini, Cl, Savoia, A., DE ROCCO, Daniela, Pujol Moix, N, Nicchia, Elena, Savoia, Anna, University of Zurich |
| المصدر: | Human Mutation, 35(2), 236-247. Wiley CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET HUMAN MUTATION r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Oncology, thrombocytopenia, Medicina Clínica, Disease, Malattia MYH9 associata, Myh9 related disease, MYH9 RELATED DISEASE, Myh9, MYH9, Risk Factors, purl.org/becyt/ford/3.2 [https], Genotype, Genetics(clinical), CRYSTAL-STRUCTURE, Age of Onset, IIA, Genetics (clinical), deafne, MYOSIN HEAVY-CHAIN, EPSTEIN-SYNDROME, Molecular Motor Proteins, FECHTNER SYNDROMES, Trombocitopenia, Penetrance, POWER STROKE STATE, Phenotype, Italy, nephropathy, Female, purl.org/becyt/ford/3 [https], Miosina No Muscular Iia, Adult, 2716 Genetics (clinical), medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, MOTOR DOMAIN, Hearing Loss, Sensorineural, Genetic counseling, 610 Medicine & health, Biology, nonmuscle myosin, Article, Cataract, Nephropathy, 1311 Genetics, Internal medicine, deafness, Genetics, medicine, Humans, Hematología, Gene, Genetic Association Studies, Hereditaria, Myosin Heavy Chains, MUTATIONS, Settore MED/09 - MEDICINA INTERNA, medicine.disease, Amino Acid Substitution, Epstein Syndrome, Mutation, 10032 Clinic for Oncology and Hematology, Linear Models, SMOOTH-MUSCLE MYOSIN |
| الوصف: | MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype–phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD. Fil: Pecci, Alessandro. University of Pavia; Italia Fil: Klersy, Catherine. IRCCS Policlinico San Matteo Foundation; Italia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Lee, Kieran J. D.. University of Leeds; Reino Unido Fil: De Rocco, Daniela. Università degli Studi di Trieste; Italia Fil: Bozzi, Valeria. University of Pavia; Italia Fil: Russo, Giovanna. University of Catania; 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: Loffredo, Giuseppe. Pausilipon Hospital. Department of Oncology; Italia Fil: Ballmaier, Matthias. Hannover Medical School; Alemania Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Beggiato, Eloise. Hospital “Città della Salute e Della Scienza”; Italia Fil: Kahr, Walter H. A.. University of Toronto; Canadá. Hospital for Sick Children. Division of Hematology/Oncology; Canadá Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Platokouki, Helen. “Aghia Sophia” Children's Hospital; Grecia Fil: Van Geet, Christel. University of Leuven. Center for Molecular and Vascular Biology; Bélgica Fil: Noris, Patrizia. University of Pavia; Italia Fil: Yerram, Preethi. University of Missouri; Estados Unidos Fil: Hermans, Cedric. St-Luc University Hospital; Bélgica Fil: Gerber, Bernhard. University Hospital Zurich, Division of Hematology; Suiza Fil: Economou, Marina. Aristotle University; Grecia Fil: De Groot, Marco. University of Groningen; Países Bajos Fil: Zieger, Barbara. University Medical Center Freiburg; Alemania Fil: De Candia, Erica. Catholic University of Rome; Italia Fil: Fraticelli, Vincenzo. Giovanni Paolo II Foundation; Italia Fil: Kersseboom, Rogier. Erasmus Medical Centre; Países Bajos Fil: Piccoli, Giorgina B.. Università di Torino; Italia Fil: Zimmermann, Stefanie. Goethe Universitat Frankfurt; Alemania Fil: Fierro, Tiziana. Università di Perugia; Italia 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: Vianello, Fabrizio. Università di Padova; Italia Fil: Zaninetti, Carlo. University of Pavia; Italia Fil: Nicchia, Elena. Università degli Studi di Trieste; Italia Fil: Güthner, Christiane. Stadtspital Triemli. Department of Medical Oncology and Hematology; Italia Fil: Baronci, Carlo. Pediatric Hospital "Bambino Gesù"; Italia Fil: Seri, Marco. Università di Bologna; Italia Fil: Knight, Peter J.. University of Leeds; Reino Unido Fil: Balduini, Carlo L.. University of Pavia; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia |
| وصف الملف: | STAMPA; application/pdf |
| اللغة: | English |
| تدمد: | 1059-7794 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0b3202308793ba3d6d45b4fe01ee6e8 https://research.rug.nl/en/publications/8f687127-8140-4108-abe8-7c14ccda866a |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e0b3202308793ba3d6d45b4fe01ee6e8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10597794 |
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