2026-04-17T06:44:11Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Gialluisi, Alessandro author Reccia, Mafalda Giovanna author Modugno, Nicola author Nutile, Teresa author Lombardi, Alessia author Di Giovannantonio, Luca Giovanni author Pietracupa, Sara author Ruggiero, Daniela author Scala, Simona author Gambardella, Stefano author Noyce, Alastair J. author Kaiyrzhanov, Rauan author Middlehurst, Ben author Kia, Demis A. author Tan, Manuela author Houlden, Henry author Morris, Huw author Plun-Favreau, Helen author Holmans, Peter author Hardy, John author Trabzuni, Daniah author Quinn, John author Bubb, Vivien author Mok, Kin Y. author Kinghorn, Kerri J. author Billingsley, Kimberley author Wood, Nicholas W. author Lewis, Patrick author Schreglmann, Sebastian author Lovering, Rruth author R'Bibo, Lea author Manzoni, Claudia author Rizig, Mie author Ryten, Mina author Guelfi, Sebastian author Escott-Price, Valentina author Chelban, Viorica author Foltynie, Thomas author Williams, Nigel author Morrison, Karen E. author Clarke, Carl author Brice, Alexis author Danjou, Fabrice author Lesage, Suzanne author Corvol, Jean-Christophe author Martinez Rande, Maria author Schulte, Claudia author Brockmann, Kathrin author Simón-Sánchez, Javier author Heutink, Peter author Rizzu, Patrizia author Sharma, Manu author Gasser, Thomas author Cookson, Mark R. author Bandres-Ciga, Sara author Blauwendraat, Cornelis author Craig, David W. author Narendra, Derek author Faghri, Faraz author Gibbs, J.Raphael author Hernandez, Dena G. author Van Keuren-Jensen, Kendall author Shulman, Joshua M. author Iwaki, Hirotaka author Leonard, Hampton L. author Nalls, Mike A. author Robak, Laurie author Bras, Jose author Guerreiro, Rita author Lubbe, Steven author Finkbeiner, Steven author Mencacci, Niccolo E. author Lungu, Codrin author Singleton, Andrew B. author Scholz, Sonja author Reed, Xylena author Alcalay, Roy N. author Gan-Or, Zin author Rouleau, Guy A. author Krohn, Lynne author van Hilten, Jacobus J. author Marinus, Johan author Adarmes-Gómez, A.D. author Aguilar Barberà, Miquel author Alvarez, Ignacio author Alvarez, Victoria author Barrero, Francisco Javier author Bergareche Yarza, Jesús Alberto author Bernal-Bernal, Inmaculada author Blázquez Estrada, Marta author Bonilla-Toribio, Marta author Botía, Juan A. author Boungiorno, María Teresa author Buiza-Rueda, Dolores author Carrillo, Fátima author Carrión-Claro, M. author Cerdan, Debora author Clarimón, Jordi author Compta, Yaroslau author Diez-Fairen, Monica author Dols Icardo, Oriol author Duarte, Jacinto author Duran, Raquel author Escamilla Sevilla, Francisco author Ezquerra, Mario author Feliz, Cici author Fernández, Manel author Fernández-Santiago, Rubén author Garcia, Ciara author García-Ruiz, Pedro author Gómez-Garre, Pilar author Gomez Heredia, Maria Jose author Gonzalez-Aramburu, Isabel author Gorostidi Pagola, Ana author Hoenicka, Janet author Infante, Jon author Jesús, Silvia author Jiménez-Escrig, Adriano author Kulisevsky, Jaime author Labrador-Espinosa, Miguel A. author Lopez-Sendon, Jose Luis author López de Munain Arregui, Adolfo author Macias, Daniel author Martínez Torres, Irene author Marín, Juan author Marti, Maria Jose author Martínez-Castrillo, Juan Carlos author Méndez-del-Barrio, Carlota author Menéndez González, Manuel author Mata, Marina author Mínguez, Adolfo author Mir, Pablo author Mondragon Rezola, Elisabet author Muñoz, Esteban author Pagonabarraga Mora, Javier author Pastor, Pau author Perez Errazquin, Francisco author Periñán-Tocino, Teresa author Ruiz-Martínez, Javier author Ruz, Clara author Sanchez Rodriguez, Antonio author Sierra, María author Suarez-Sanmartin, Esther author Tabernero, Cesar author Tartari, Juan Pablo author Tejera-Parrado, Cristina author Tolosa, Eduard author Valldeoriola, Francesc author Vargas-González, Laura author Vela, Lydia author Vives, Francisco author Zimprich, Alexander author Pihlstrom, Lasse author Toft, Mathias author Koks, Sulev author Taba, Pille author Hassin-Baer, Sharon author Majamaa, Kari author Siitonen, Ari author Okubadejo, Njideka U. author Ojo, Oluwadamilola O. author Shashkin, Chingiz author Zharkynbekova, Nazira author Akhmetzhanov, Vadim author Aitkulova, Akbota author Zholdybayeva, Elena author Zharmukhanov, Zharkyn author Kaishybayeva, Gulnaz author Karimova, Altynay author Sadykova, Dinara author Iacoviello, Licia author Gianfrancesco, F. author Acampora, D. author D'Esposito, M. author Simeone, A. author Ciullo, Marina author Esposito, T. author 2021 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 (. Late onset Parkinson's disease Whole exome sequencing Novel candidate genes for Parkinson's disease Rare variant burden analysis Identification of sixteen novel candidate genes for late onset Parkinson's disease