Nicolas, Gaël
Mayo Clinic
Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, UNIROUEN, INSERM U1245 and Rouen University Hospital, Normandie University, F 76000 Rouen, France.
Citations 3
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Guen, Yann Le , Luo, Guo , Damotte, Vincent , Jansen, Iris E. , Nicolas, Aude , Rojas, Itziar de, Bellenguez, Céline , Lian, Michelle Mulan , Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier‐Boley, Benjamin , Naito, Tatsuhiko , Talyansky, Seth D., Yogeshwar, Selina , Sempere, Vicente Peris, Satake, Wataru , Álvarez, Victoria , Arosio, Beatrice , Boland, Anne , Daniele, Antonio , Darling, D.H., Dichgans, Martin , Dufouil, Carole , Düzel, Emrah , García‐Ribas, Guillermo, García‐Alberca, José María , García-González, Pablo, Giedraitis, Vilmantas , Graff, Caroline , Grünblatt, Edna , Hausner, Lucrezia , Jung, Yoo Jin , Deckert, Jürgen, Kern, Silke , Kuulasmaa, Teemu , Lee, Kun Ho , Lin, Ling , Masullo, Carlo , Mehrabian, Shima , Mendonça, Alexandre de , Boada, Merçé , Mir, Pablo , Moreno, Fermín , Nicolas, Gaël , Niida, Shumpei , Nordestgaard, Børge G. , Papenberg, Goran, Papma, Janne M., Pástor, Pau , Peters, Oliver , Popp, Julius , Molina‐Porcel, Laura , Puerta, Raquel , Pérez‐Tur, Jordi , Ramakers, Inez H.G.B. , Real, Luís Miguel , Riedel‐Heller, Steffi G. , Rodríguez‐Rodríguez, Eloy , Ross, Owen A. , Scarmeas, Nikolaos , Schneider, Anja , Solfrizzi, Vincenzo , Spalletta, Gianfranco , Tan, Eng‐King , Tegos, Thomas, Thomassen, Jesper Qvist , Tremolizzo, Lucio , Verhey, Frans, EADB, group, GR@ACE study, DemGene, EADI, GERAD, Blennow, Kaj , He, Zihuai , Jessen, Frank , Kehoe, Patrick G. , Duin, Cornelia van, Sánchez‐Juan, Pascual , Zettergren, Anna , Okada, Yukinori , Rossi, Giacomina, Gim, Jungsoo , Sims, Rebecca, Ramı́rez, Alfredo , Lambert, Jean‐Charles , Greicius, Michael D. , Mignot, Emmanuel , Moreno–Grau, Sonia , Rojas, Itziar de, Prokic, Ivana, Aarsland, Dag, García‐González, Pablo , Abdelnour, Carla , Armstrong, Nicola J. , Anthoula, Tsolaki, Archetti, Silvana, Pastor, Alfonso Arias, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa , Baquero, Miquel , Pastor, Ana Belén , Besse, Céline , Bizarro, Alessandra, Blesa, Rafael , Bossù, Paola , Brusco, Luis Ignacio , Buiza‐Rueda, Dolores, Bürger, Katharina , Burholt, Vanessa, Cecchetti, Roberta, Chillotti, Caterina , Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher , Costantini, Emanuele Maria , Daian, Delphine , Dartigues, Jean‐François, Escott-Price, Valentina, Ewers, Michael , Fernández‐Fuertes, Marta , Ferreira, Catarina B. , Fin, Bertrand, Fließbach, Klaus , Franco-Macías, Emlio, García-González, Pablo, García‐Madrona, Sebastián, Giegling, Ina, Giorgio, Giaccone, González-Pérez, Antonio, Grande, Giulia , Green, Emma , Grimmer, Timo, Hardy, John, Hartmann, Annette M. , Harwood, Janet , Helisalmi, Seppo , Hernández, Isabel, Hoffmann, Per, Vilas, Raquel Huerto, Hulsman, Marc , Johansson, Charlotte , Kilander, Lena, Ståhlbom, Anne Kinhult, Koivisto, Anne M. , Lage, Carmen , Lerch, Ondřej , Munain, Adolfo Lopez de, Löwemark, Malin, Luckcuck, Lauren, Maier, Wolfgang, Marco, Spallazzi, Montes, Ángel Martín, Rodríguez, Carmen Martínez, Meggy, Alun, Mendoza, Silvia, Moebus, Susanne, Morelli, Laura , Möthen, Markus M., Muchnik, Carolina , Orsini, Michela, Péricard, Pierre , Piñol-Ripoll, Gerard, Polak, Thomas, Quenez, Olivier , Rábano, Alberto , Ramakers, Inez, Riederer, Peter, Rongve, Arvid, Allende, Irene Rosas, Rujescu, Dan, Sakka, Paraskevi , Sánchez‐Arjona, María Bernal, Sando, Sigrid Botne , Scamosci, Michela, Scherbaum, Norbert, Scherer, Martin, Schott, Jonathan M., Shadrin, Alexey A, Skrobot, Olivia Anna, Solfrizzi, Vincenzo, Spottke, Annika , Stordal, Eystein , Tartan, Juan Pablo, Traykov, Latchezar , Tybjærg‐Hansen, Anne, Ullgren, Abbe, Ulstein, Ingun, Dongen, Jasper Van , Wallon, David, Windle, Gill, Woods, Bob , Zulaica, Miren , Laczó, Jan , Maťoška, Václav , Piras, Federica, Ciullo, Valentina , Shofany, Jacob, Andreoni, Simona, Zompo, Maria Del, Bastiani, Patrizia, Natunen, Teemu , Antikaínen, Riitta , Abraham, Richard, Al-Chalabi, Ammar, Brayne, Carol, Brown, Kristelle S., Collinge, John, Craig, David W. , Deloukas, Pangiotis, Gerrish, Amy, 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Sanchez del Valle, Sánchez‐Juan, Pascual, Sastre, Isabel , Valero, S, Vicente, MP, Vigo-Ortega, R, Shadrin, Alexey A, Rongve, Arvid, Bosnes, Ingunn , Athanasiu, Lavinia, Aarsland, Dag, Andreassen, Ole A., Epelbaum, Jacques, Wallon, David, Hannequin, Didier , Campion, Dominique , Dermecourt, Vincent, Dubois, Bruno , Amouyel, Phillippe, Sims, Rebecca, Gerrish, Amy, Thomas, Charlene , Meggy, Alun, Davies, Chloe, Dowzell, Kimberley, Bernardo-Harrington, Mateus, Hoffmann, Per, Brown, Kristelle, Schott, Jonathan M., Rossor, Martin, Ryan, Natalie S. , Uphill, James, Al-Chalabi, Ammar, Bass, Nick, Abraham, Richard, Kölsch, Heike, Schürmann, Britta, Lacour, ndré, Herold, Christine, Johnston, Janet, Todd, Stephen, Proitsi, Petra, Patel, Yogen, Warden, Donald, Wilcock, Gordon , Clarke, Robert , Lawlor, Brian, McQuillin, Andrew, Hardy, John, Brayne, Carol, Deloukas, Panagiotis, Sussams, Rebecca, Warner, Nick, Bayer, Anthony, Singleton, Andrew, Rujescu, Dan, Giegling, Ina, Klopp, Norman, Mayhaus, 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Molina-Porcel, Laura , de Mendonça, Alexandre , Graff, Caroline , Ambati, Aditya , Yu, Eric , Rojas, Itziar de, Leal, Thiago Peixoto , Miyashita, Akinori , Küçükali, Fahri , Belloy, Michaël E. , Benussi, Luisa , Borroni, Barbara , Bullido, María J. , Caffarra, Paolo , Clarimón, Jordi , Darling, Daniel, Debette, Stéphanie , Deleuze, Jean‐François , Galimberti, Daniela , García-González, Pablo, Goldhardt, Oliver , Hanon, Olivier , Heilmann‐Heimbach, Stefanie , Holstege, Henne H. , Hort, Jakub , Mecocci, Patrizia , Moebus, Susanne , Nacmias, Benedetta , Parnetti, Lucilla , Pasquier, Florence , Pijnenburg, Yolande A.L. , Piñol‐Ripoll, Gerard , Rainero, Innocenzo , Royo, José Luís , Scheltens, Philip , Scherbaum, Norbert , Seripa, Davide , Skoog, Ingmar , Squassina, Alessio , Swieten, John C. van , Sánchez‐Valle, Raquel , Teunissen, Charlotte E. , Vyhnálek, Martin , Wærn, Margda , Wiltfang, Jens , Zhang, Jing , EADB, group, GR@ACE study, DemGene, EADI, GERAD, Zetterberg, Henrik , Williams, 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Meggy, Alun, Menéndez‐González, Manuel , Moebus, Susanne, Mol, Merel O. , Montrreal, Laura , Morgan, Kevin , Ngandu, Tiia , Olaso, Robert , Orellana, Adelina , Ortega, Gemma , Padovani, Alessandro , Pérez‐Cordón, Alba , Pineda, Juan Antonio , Piñol-Ripoll, Gerard, Pisanu, Claudia , Posthuma, Daniëlle , Priller, Josef , Quintela, Inés , Reinders, Marcel J. T. , Roberto, Natalia , Rongve, Arvid, Rosende‐Roca, Maitée , Rubino, Elisa , Rujescu, Dan, Sáez, María Eugenia , Saltvedt, Ingvild Tina , Sanabria, Ángela , Sánchez-García, Florentino , Scarpini, Elio , Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias C. , Schott, Jonathan M., Selbæk, Geir , Shadrin, Alexey A, Soininen, Hilkka S. , Solfrizzi, Vincenzo, Solomon, Alina , Sorbi, Sandro , Sotolongo‐Grau, Óscar , Tárraga, Lluís , Tesi, Niccoló , Thalamuthu, Anbupalam , Uitterlinden, André G. , Valero, Sergi , Lugt, Aad van der , Rooij, Jeroen van , Vandenberghe, Rik , Vidal, Jean‐Sébastien , Vogelgsang, Jonathan S. , Wagner, Michael , Wallon, David , Weinhold, Leonie , Yannakoulia, Mary , Serpente, María , Assogna, Francesca , Piras, Fabrizio , Piras, Federica, Ferrarese, Carlo , Sala, Gessica , Zoia, C , Benussi, Alberto , Takalo, Mari , Laatikainen, Tiina K. , Tuomi, Tiinamaija , Strandberg, Timo E. , Lindström, Jaana , Peltonen, Markku , Abraham, Richard, Al-Chalabi, Ammar, Bass, Nicholas , Brayne, Carol, Gerrish, Amy, Gill, Michael , Harold, Denise , Lawlor, Brian, Livingston, Gill , Lovestone, Simon , Lupton, Michelle K. , Mann, David , McGuinness, Bernadette , McQuillin, Andrew, O‘Donovan, Michael , Powell, John , Proitsi, Petra, Rossor, Martin, Shaw, Christopher E. , Smith, A. David , Todd, Stephen, Macías‐García, Daniel , Carrillo, F, Vargas, Liliana , Marín, M, Alonso, María Dolores, Gómez-Garre, P, Cañabate, Pilar , Escuela, R, Vigo-Ortega, R, Jesús, Silvia , Vacca, Alessandro , Roveta, Fausto , Boecker, Henning , Perneczky, Robert , Anastasiou, Costas Anastasios , Malik, Rainer , Parveen, Kayenat, Mihova, Kalina Yonkova , Weber, Heike , Kochen, Silvia , Saenz, Aldo, Kohler, Matias, Novack, Gisela Vanina , Tagliavini, Fabrizio , Nielsen, Sune Fallgaard, Fenoglio, Chiara , Biessels, Geert Jan , Love, Seth , Broeckhoven, Christine Van , Rubinsztein, David Chaim , Teipel, Stefan Johannes , Deramecourt, Vincent , Martínez-Larrad, María Teresa, Ghanbari, Mohsen , Mather, Karen A. , Ikram, M. Arfan , Rossi, Giacomina, Andreassen, Ole A., Duijn, Cornelia M. van , Alarcon, E, Buendia, M, Cano, Amanda C. , Anchuelo, Arturo Corbatón , Macı́as, Juan , Maroñas, Olalla , Martín, E, Martínez, MT, Marquié, M, Moreno, M. , Núñez‐Llaves, Raúl , Olivé, C, Puerta, R, Serrano‐Ríos, Manuel , Valero, S, Bernal, M, Carrillo, F, Pancorbo, Marian M. de , Escuela, R, Gómez-Garre, P, Munaín, Adolfo López de , Manzanares, Salvadora , Marín, M, Marquié, M, Martínez, B, Martínez, C, Martínez, V, Álvarez, A Martínez-Lage, Iriarte, M Mendioroz, Tur, J. 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Proceedings of the National Academy of Sciences | August 29, 2023 | Volume: 120 | Issue: 36 | Pages: No page available
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
Variants in CLDN5 cause a syndrome characterized by seizures, microcephaly and brain calcifications
Deshwar, Ashish R. , Cytrynbaum, Cheryl , Murthy, Harsha, Zon, Jessica, Volpatti, Jonathan, Newbury‐Ecob, Ruth , Yu, Emily, Walker, Suzi, Scherer, Stephen W. , Mahida, Sonal , Elitt, Christopher M. , Nicolas, Gaël , Goldenberg, Alice , Saugier-Véber, Pascale , Lecoquierre, François , Dabaj, Ivana , Meddaugh, Hannah, Marble, Michael , Keppler‐Noreuil, Kim M. , Drayson, Lucy, Barañano, Kristin , Chassevent, Anna , Agre, Katie, Létard, Pascaline , Laquerrière, Annie, Ramsey, Keri , Henderson, Lindsay B. , Brady, Lauren , Tarnopolsky, Mark A. , Bainbridge, Matthew N. , Friedman, Jennifer , Capri, Yline , Athayde, Larissa Sampaio de, Ramos, Luiza , Blaser, Susan , Scherer, Stephen W , Nicolas, Gaël , Dabaj, Ivana , Dowling, James J , Lecoquierre, Francois , Tarnopolsky, Mark , Chitayat, David A. , Ellard, Sian , Allen, Hana Lango , Noche, Ramil R. , Bilan, Frédéric , Guyader, Gwenaël Le , Kok, Fernando , Gurgel‐Giannetti, Juliana , Weksberg, Rosanna
Brain | December 8, 2022 | Volume: 146 | Issue: 6 | Pages: 2285-2297
Abstract The blood–brain barrier ensures CNS homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity of the blood–brain barrier. We have identified de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications. All variants clustered in one subregion/domain of the CLDN5 gene and the recurrent variants demonstrate genotype–phenotype correlations. We modelled both patient variants and loss of function alleles in the zebrafish to show that the variants analogous to those in patients probably result in a novel aberrant function in CLDN5. In total, human patient and zebrafish data provide parallel evidence that pathogenic sequence variants in CLDN5 cause a novel neurodevelopmental disorder involving disruption of the blood–brain barrier and impaired neuronal function.
Brain calcifications and PCDH12 variants
Nicolas, Gaël , Ramos, Eliana Marisa , Lemos, Roberta R., Ferreira, Joana , Moura, Denis A. P. , Sobrido, María Jesús, Richard, Anne‐Claire, Lopez, Alma Rosa, Legati, Andrea , Deleuze, Jean‐François , Boland, Anne , Quenez, Olivier , Krystkowiak, Pierre, Favrole, Pascal, Geschwind, Daniel H. , Aran, Adi , Segel, Reeval , Levy‐Lahad, Ephrat , Coppola, Giovanni , Rademakers, Rosa , Oliveira, João Ricardo Mendes de , Moura, Denis, Sobrido, Maria J, Levy-Lahad, Ephrat, de Oliveira, João R M, Sánchez-Contreras, Mónica , Dickson, Dennis W. , Nicolas, Gaël
Neurology Genetics | July 27, 2017 | Volume: 3 | Issue: 4 | Pages: No page available