2026-04-13T00:49:22Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4663432026-03-28T08:23:10Zcom_2072_98col_2072_378192

urn:hdl:2072/466343 Identification of sixteen novel candidate genes for late onset Parkinson's disease Gialluisi, Alessandro Reccia, Mafalda Giovanna Modugno, Nicola Nutile, Teresa Lombardi, Alessia Di Giovannantonio, Luca Giovanni Pietracupa, Sara Ruggiero, Daniela Scala, Simona Gambardella, Stefano Noyce, Alastair J. Kaiyrzhanov, Rauan Middlehurst, Ben Kia, Demis A. Tan, Manuela Houlden, Henry Morris, Huw Plun-Favreau, Helen Holmans, Peter Hardy, John Trabzuni, Daniah Quinn, John Bubb, Vivien Mok, Kin Y. Kinghorn, Kerri J. Billingsley, Kimberley Wood, Nicholas W. Lewis, Patrick Schreglmann, Sebastian Lovering, Rruth R'Bibo, Lea Manzoni, Claudia Rizig, Mie Ryten, Mina Guelfi, Sebastian Escott-Price, Valentina Chelban, Viorica Foltynie, Thomas Williams, Nigel Morrison, Karen E. Clarke, Carl Brice, Alexis Danjou, Fabrice Lesage, Suzanne Corvol, Jean-Christophe Martinez Rande, Maria Schulte, Claudia Brockmann, Kathrin Simón-Sánchez, Javier Heutink, Peter Rizzu, Patrizia Sharma, Manu Gasser, Thomas Cookson, Mark R. Bandres-Ciga, Sara Blauwendraat, Cornelis Craig, David W. Narendra, Derek Faghri, Faraz Gibbs, J.Raphael Hernandez, Dena G. Van Keuren-Jensen, Kendall Shulman, Joshua M. Iwaki, Hirotaka Leonard, Hampton L. Nalls, Mike A. Robak, Laurie Bras, Jose Guerreiro, Rita Lubbe, Steven Finkbeiner, Steven Mencacci, Niccolo E. Lungu, Codrin Singleton, Andrew B. Scholz, Sonja Reed, Xylena Alcalay, Roy N. Gan-Or, Zin Rouleau, Guy A. Krohn, Lynne van Hilten, Jacobus J. Marinus, Johan Adarmes-Gómez, A.D. Aguilar Barberà, Miquel Alvarez, Ignacio Alvarez, Victoria Barrero, Francisco Javier Bergareche Yarza, Jesús Alberto Bernal-Bernal, Inmaculada Blázquez Estrada, Marta Bonilla-Toribio, Marta Botía, Juan A. Boungiorno, María Teresa Buiza-Rueda, Dolores Carrillo, Fátima Carrión-Claro, M. Cerdan, Debora Clarimón, Jordi Compta, Yaroslau Diez-Fairen, Monica Dols Icardo, Oriol Duarte, Jacinto Duran, Raquel Escamilla Sevilla, Francisco Ezquerra, Mario Feliz, Cici Fernández, Manel Fernández-Santiago, Rubén Garcia, Ciara García-Ruiz, Pedro Gómez-Garre, Pilar Gomez Heredia, Maria Jose Gonzalez-Aramburu, Isabel Gorostidi Pagola, Ana Hoenicka, Janet Infante, Jon Jesús, Silvia Jiménez-Escrig, Adriano Kulisevsky, Jaime Labrador-Espinosa, Miguel A. Lopez-Sendon, Jose Luis López de Munain Arregui, Adolfo Macias, Daniel Martínez Torres, Irene Marín, Juan Marti, Maria Jose Martínez-Castrillo, Juan Carlos Méndez-del-Barrio, Carlota Menéndez González, Manuel Mata, Marina Mínguez, Adolfo Mir, Pablo Mondragon Rezola, Elisabet Muñoz, Esteban Pagonabarraga Mora, Javier Pastor, Pau Perez Errazquin, Francisco Periñán-Tocino, Teresa Ruiz-Martínez, Javier Ruz, Clara Sanchez Rodriguez, Antonio Sierra, María Suarez-Sanmartin, Esther Tabernero, Cesar Tartari, Juan Pablo Tejera-Parrado, Cristina Tolosa, Eduard Valldeoriola, Francesc Vargas-González, Laura Vela, Lydia Vives, Francisco Zimprich, Alexander Pihlstrom, Lasse Toft, Mathias Koks, Sulev Taba, Pille Hassin-Baer, Sharon Majamaa, Kari Siitonen, Ari Okubadejo, Njideka U. Ojo, Oluwadamilola O. Shashkin, Chingiz Zharkynbekova, Nazira Akhmetzhanov, Vadim Aitkulova, Akbota Zholdybayeva, Elena Zharmukhanov, Zharkyn Kaishybayeva, Gulnaz Karimova, Altynay Sadykova, Dinara Iacoviello, Licia Gianfrancesco, F. Acampora, D. D'Esposito, M. Simeone, A. Ciullo, Marina Esposito, T. Late onset Parkinson's disease Whole exome sequencing Novel candidate genes for Parkinson's disease Rare variant burden analysis Altres ajuts: Italian Ministry of Health grant (RF 2019-12370224, GR2016-02362247); Italian Ministry of Economic Development (F/0009/00X26); Fondazione Umberto Veronesi. Background: Parkinson's disease (PD) is a neurodegenerative movement disorder affecting 1-5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD. Methods: The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls). Results: Family-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (. 2021 Article Molecular neurodegeneration ; Vol. 16 Núm. 1 (december 2021), p. 35 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/