Author: "Courtin, Thomas" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Courtin, Thomas"' showing total 136 results

Start Over Author "Courtin, Thomas"

136 results on '"Courtin, Thomas"'

1. Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis

Author: Cogan, Guillaume, Zaki, Maha S., Issa, Mahmoud, Keren, Boris, Guillaud-Bataille, Marine, Renaldo, Florence, Isapof, Arnaud, Lallemant, Pauline, Stevanin, Giovanni, Guillot-Noel, Lena, Courtin, Thomas, Buratti, Julien, Freihuber, Cécile, Gleeson, Joseph G., Howarth, Robyn, Durr, Alexandra, de Sainte Agathe, Jean-Madeleine, and Mignot, Cyril
Published: 2024
Full Text: View/download PDF

2. Genetic heterogeneity in familial forms of genetic generalized epilepsy: from mono- to oligogenism

Author: Dahawi, Maha, de Sainte Agathe, Jean-Madeleine, Elmagzoub, Mohamed S., Ahmed, Elhami A., Buratti, Julien, Courtin, Thomas, Noé, Eric, Bogoin, Julie, Copin, Bruno, Elmugadam, Fatima A., Abdelgadir, Wasma A., Ahmed, Ahmed K. M. A., Daldoum, Mohamed A., Altayeb, Rayan Mamoon Ibrahim, Bashir, Mohamed, Khalid, Leena Mohamed, Gamil, Sahar, Baldassari, Sara, Elsayed, Liena, Keren, Boris, Nuel, Gregory, Ahmed, Ammar E., and Leguern, Eric
Published: 2024
Full Text: View/download PDF

3. Genotype–phenotype correlation in PRKN-associated Parkinson’s disease

Author: Menon, Poornima Jayadev, Sambin, Sara, Criniere-Boizet, Baptiste, Courtin, Thomas, Tesson, Christelle, Casse, Fanny, Ferrien, Melanie, Mariani, Louise-Laure, Carvalho, Stephanie, Lejeune, Francois-Xavier, Rebbah, Sana, Martet, Gaspard, Houot, Marion, Lanore, Aymeric, Mangone, Graziella, Roze, Emmanuel, Vidailhet, Marie, Aasly, Jan, Gan Or, Ziv, Yu, Eric, Dauvilliers, Yves, Zimprich, Alexander, Tomantschger, Volker, Pirker, Walter, Álvarez, Ignacio, Pastor, Pau, Di Fonzo, Alessio, Bhatia, Kailash P., Magrinelli, Francesca, Houlden, Henry, Real, Raquel, Quattrone, Andrea, Limousin, Patricia, Korlipara, Prasad, Foltynie, Thomas, Grosset, Donald, Williams, Nigel, Narendra, Derek, Lin, Hsin-Pin, Jovanovic, Carna, Svetel, Marina, Lynch, Timothy, Gallagher, Amy, Vandenberghe, Wim, Gasser, Thomas, Brockmann, Kathrin, Morris, Huw R., Borsche, Max, Klein, Christine, Corti, Olga, Brice, Alexis, Lesage, Suzanne, and Corvol, Jean Christophe
Published: 2024
Full Text: View/download PDF

4. Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration.

Author: Conti, Valerio, Giubbolini, Simone, Barrick, Rebekah, Bergant, Gaber, Writzl, Karin, Bijlsma, Emilia, Brunet, Theresa, Cacheiro, Pilar, Mei, Davide, Devlin, Anita, Hoffer, Mariëtte, Machol, Keren, Mannaioni, Guido, Sakamoto, Masamune, Menezes, Manoj, Courtin, Thomas, Sherr, Elliott, Parra, Riccardo, Richardson, Ruth, Roscioli, Tony, Scala, Marcello, von Stülpnagel, Celina, Smedley, Damian, Torella, Annalaura, Tohyama, Jun, Koichihara, Reiko, Hamada, Keisuke, Ogata, Kazuhiro, Suzuki, Takashi, Sugie, Atsushi, van der Smagt, Jasper, van Gassen, Koen, Valence, Stephanie, Vittery, Emma, Malone, Stephen, Kato, Mitsuhiro, Matsumoto, Naomichi, Ratto, Gian, Guerrini, Renzo, Vetro, Annalisa, Pelorosso, Cristiana, Balestrini, Simona, Masi, Alessio, Hambleton, Sophie, and Argilli, Emanuela
Subjects: abnormal myelination, epilepsy, epileptic encephalopathy, hemolytic anemia, infantile spasms, ion channels, leak cation currents, osmotic stress, white matter abnormality, Humans, Brain Diseases, Ion Channels, Brain, Intellectual Disability, Phenotype
Abstract: By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense, including the recurrent p.Val44Met in 7/17 individuals, or in-frame, all affecting conserved residues located in transmembrane regions of the protein. In 12 individuals, hematological abnormalities co-occurred, such as macrocytosis and hemolysis, requiring blood transfusions in some. We modeled six variants (p.Val44Met, p.Arg433His, p.Thr481Asn, p.Gly580Ser, p.Arg660Thr, and p.Phe697Leu), each affecting a distinct transmembrane domain of the channel, in transfected Neuro2a cells and demonstrated inward leak cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca2+ transients generated under hypo-osmotic stimulation. Ectopic expression of the p.Val44Met and p.Gly580Cys variants in Drosophila resulted in early death. TMEM63B-associated DEE represents a recognizable clinicopathological entity in which altered cation conductivity results in a severe neurological phenotype with progressive brain damage and early-onset epilepsy associated with hematological abnormalities in most individuals.
Published: 2023

5. Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling.

Author: Holtz, Alexander, VanCoillie, Rachel, Vansickle, Elizabeth, Carere, Deanna, Withrow, Kara, Torti, Erin, Juusola, Jane, Millan, Francisca, Person, Richard, Guillen Sacoto, Maria, Si, Yue, Wentzensen, Ingrid, Pugh, Jada, Vasileiou, Georgia, Rieger, Melissa, Reis, André, Aldinger, Kimberly, Dobyns, William, Brunet, Theresa, Hoefele, Julia, Wagner, Matias, Haber, Benjamin, Kotzaeridou, Urania, Keren, Boris, Heron, Delphine, Mignot, Cyril, Heide, Solveig, Courtin, Thomas, Buratti, Julien, Murugasen, Serini, Donald, Kirsten, OHeir, Emily, Moody, Shade, Kim, Katherine, Burton, Barbara, Yoon, Grace, Campo, Miguel, Masser-Frye, Diane, Kozenko, Mariya, Parkinson, Christina, Sell, Susan, Gordon, Patricia, Prokop, Jeremy, Karaa, Amel, Bupp, Caleb, Raby, Benjamin, Sherr, Elliott, and Argilli, Emanuela
Subjects: Hedgehog signaling, MYH10, Neurodevelopmental disorder, Nonmuscle myosin, Primary cilia, Actins, Cilia, Hedgehog Proteins, Humans, Myosin Heavy Chains, Neurodevelopmental Disorders, Nonmuscle Myosin Type IIB
Abstract: PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10. METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis. RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems and were recapitulated in animal models of altered MYH10 activity. Variants were typically de novo missense changes with clustering observed in the motor domain. MYH10 knockout cells showed defects in primary ciliogenesis and reduced ciliary length with impaired Hedgehog signaling. MYH10 variant overexpression produced a dominant-negative effect on ciliary length. CONCLUSION: These data presented a novel genetic cause of isolated and syndromic neurodevelopmental disorders related to heterozygous variants in the MYH10 gene with implications for disrupted primary cilia length control and altered Hedgehog signaling in disease pathogenesis.
Published: 2022

6. Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect

Author: Yang, Fang, Begemann, Anais, Reichhart, Nadine, Haeckel, Akvile, Steindl, Katharina, Schellenberger, Eyk, Sturm, Ronja Fini, Barth, Magalie, Bassani, Sissy, Boonsawat, Paranchai, Courtin, Thomas, Delobel, Bruno, Gunning, Boudewijn, Hardies, Katia, Jennesson, Mélanie, Legoff, Louis, Linnankivi, Tarja, Prouteau, Clément, Smal, Noor, Spodenkiewicz, Marta, Toelle, Sandra P., Van Gassen, Koen, Van Paesschen, Wim, Verbeek, Nienke, Ziegler, Alban, Zweier, Markus, Horn, Anselm H.C., Sticht, Heinrich, Lerche, Holger, Weckhuysen, Sarah, Strauß, Olaf, and Rauch, Anita
Published: 2024
Full Text: View/download PDF

7. The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant

Author: Aerden, Mio, Denommé-Pichon, Anne-Sophie, Bonneau, Dominique, Bruel, Ange-Line, Delanne, Julian, Gérard, Bénédicte, Mazel, Benoît, Philippe, Christophe, Pinson, Lucile, Prouteau, Clément, Putoux, Audrey, Tran Mau-Them, Frédéric, Viora-Dupont, Éléonore, Vitobello, Antonio, Ziegler, Alban, Piton, Amélie, Isidor, Bertrand, Francannet, Christine, Maillard, Pierre-Yves, Julia, Sophie, Philippe, Anais, Schaefer, Elise, Koene, Saskia, Ruivenkamp, Claudia, Hoffer, Mariette, Legius, Eric, Theunis, Miel, Keren, Boris, Buratti, Julien, Charles, Perrine, Courtin, Thomas, Misra-Isrie, Mala, van Haelst, Mieke, Waisfisz, Quinten, Wieczorek, Dagmar, Schmetz, Ariane, Herget, Theresia, Kortüm, Fanny, Lisfeld, Jasmin, Debray, François-Guillaume, Bramswig, Nuria C., Atallah, Isis, Fodstad, Heidi, Jouret, Guillaume, Almoguera, Berta, Tahsin-Swafiri, Saoud, Santos-Simarro, Fernando, Palomares-Bralo, Maria, López-González, Vanesa, Kibaek, Maria, Tørring, Pernille M., Renieri, Alessandra, Bruno, Lucia Pia, Õunap, Katrin, Wojcik, Monica, Hsieh, Tzung-Chien, Krawitz, Peter, and Van Esch, Hilde
Published: 2023
Full Text: View/download PDF

8. Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

Author: Pochiero, Francesca, Mari, Francesco, Ramesh, Venkateswaran, Capra, Valeria, Mancardi, Margherita, Keren, Boris, Mignot, Cyiril, Lulli, Matteo, Parks, Kendall, Griffin, Helen, Brugger, Melanie, Nigro, Vincenzo, Hirata, Yuko, Koichihara, Reiko, Peterlin, Borut, Maki, Ryuto, Nitta, Yohei, Ambrose, John C., Arumugam, Prabhu, Bevers, Roel, Bleda, Marta, Boardman-Pretty, Freya, Boustred, Christopher R., Brittain, Helen, Brown, Matthew A., Caulfield, Mark J., Chan, Georgia C., Giess, Adam, Griffin, John N., Hamblin, Angela, Henderson, Shirley, Hubbard, Tim J.P., Jackson, Rob, Jones, Louise J., Kasperaviciute, Dalia, Kayikci, Melis, Kousathanas, Athanasios, Lahnstein, Lea, Lakey, Anna, Leigh, Sarah E.A., Leong, Ivonne U.S., Lopez, Javier F., Maleady-Crowe, Fiona, McEntagart, Meriel, Minneci, Federico, Mitchell, Jonathan, Moutsianas, Loukas, Mueller, Michael, Murugaesu, Nirupa, Need, Anna C., O’Donovan, Peter, Odhams, Chris A., Patch, Christine, Perez-Gil, Daniel, Pereira, Marina B., Pullinger, John, Rahim, Tahrima, Rendon, Augusto, Rogers, Tim, Savage, Kevin, Sawant, Kushmita, Scott, Richard H., Siddiq, Afshan, Sieghart, Alexander, Smith, Samuel C., Sosinsky, Alona, Stuckey, Alexander, Tanguy, Mélanie, Taylor Tavares, Ana Lisa, Thomas, Ellen R.A., Thompson, Simon R., Tucci, Arianna, Welland, Matthew J., Williams, Eleanor, Witkowska, Katarzyna, Wood, Suzanne M., Zarowiecki, Magdalena, Vetro, Annalisa, Pelorosso, Cristiana, Balestrini, Simona, Masi, Alessio, Hambleton, Sophie, Argilli, Emanuela, Conti, Valerio, Giubbolini, Simone, Barrick, Rebekah, Bergant, Gaber, Writzl, Karin, Bijlsma, Emilia K., Brunet, Theresa, Cacheiro, Pilar, Mei, Davide, Devlin, Anita, Hoffer, Mariëtte J.V., Machol, Keren, Mannaioni, Guido, Sakamoto, Masamune, Menezes, Manoj P., Courtin, Thomas, Sherr, Elliott, Parra, Riccardo, Richardson, Ruth, Roscioli, Tony, Scala, Marcello, von Stülpnagel, Celina, Smedley, Damian, Torella, Annalaura, Tohyama, Jun, Hamada, Keisuke, Ogata, Kazuhiro, Suzuki, Takashi, Sugie, Atsushi, van der Smagt, Jasper J., van Gassen, Koen, Valence, Stephanie, Vittery, Emma, Malone, Stephen, Kato, Mitsuhiro, Matsumoto, Naomichi, Ratto, Gian Michele, and Guerrini, Renzo
Published: 2023
Full Text: View/download PDF

9. Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases

Author: Marcogliese, Paul C., Deal, Samantha L., Andrews, Jonathan, Harnish, J. Michael, Bhavana, V. Hemanjani, Graves, Hillary K., Jangam, Sharayu, Luo, Xi, Liu, Ning, Bei, Danqing, Chao, Yu-Hsin, Hull, Brooke, Lee, Pei-Tseng, Pan, Hongling, Bhadane, Pradnya, Huang, Mei-Chu, Longley, Colleen M., Chao, Hsiao-Tuan, Chung, Hyung-lok, Haelterman, Nele A., Kanca, Oguz, Manivannan, Sathiya N., Rossetti, Linda Z., German, Ryan J., Gerard, Amanda, Schwaibold, Eva Maria Christina, Fehr, Sarah, Guerrini, Renzo, Vetro, Annalisa, England, Eleina, Murali, Chaya N., Barakat, Tahsin Stefan, van Dooren, Marieke F., Wilke, Martina, van Slegtenhorst, Marjon, Lesca, Gaetan, Sabatier, Isabelle, Chatron, Nicolas, Brownstein, Catherine A., Madden, Jill A., Agrawal, Pankaj B., Keren, Boris, Courtin, Thomas, Perrin, Laurence, Brugger, Melanie, Roser, Timo, Leiz, Steffen, Mau-Them, Frederic Tran, Delanne, Julian, Sukarova-Angelovska, Elena, Trajkova, Slavica, Rosenhahn, Erik, Strehlow, Vincent, Platzer, Konrad, Keller, Roberto, Pavinato, Lisa, Brusco, Alfredo, Rosenfeld, Jill A., Marom, Ronit, Wangler, Michael F., and Yamamoto, Shinya
Published: 2022
Full Text: View/download PDF

10. Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, Jr, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Published: 2022
Full Text: View/download PDF

11. Phenotype associated with TAF2 biallelic mutations: A clinical description of four individuals and review of the literature

Author: Lesieur-Sebellin, Marion, Capri, Yline, Grisval, Margot, Courtin, Thomas, Burtz, Augustine, Thevenon, Julien, Buratti, Julien, Lejeune, Elodie, Faivre, Laurence, and Keren, Boris
Published: 2021
Full Text: View/download PDF

12. Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Author: Harris, Holly K., Nakayama, Tojo, Lai, Jenny, Zhao, Boxun, Argyrou, Nikoleta, Gubbels, Cynthia S., Soucy, Aubrie, Genetti, Casie A., Suslovitch, Victoria, Rodan, Lance H., Tiller, George E., Lesca, Gaetan, Gripp, Karen W., Asadollahi, Reza, Hamosh, Ada, Applegate, Carolyn D., Turnpenny, Peter D., Simon, Marleen E.H., Volker-Touw, Catharina M.L., Gassen, Koen L.I. van, Binsbergen, Ellen van, Pfundt, Rolph, Gardeitchik, Thatjana, Vries, Bert B.A. de, Immken, LaDonna L., Buchanan, Catherine, Willing, Marcia, Toler, Tomi L., Fassi, Emily, Baker, Laura, Vansenne, Fleur, Wang, Xiadong, Ambrus, Julian L., Jr., Fannemel, Madeleine, Posey, Jennifer E., Agolini, Emanuele, Novelli, Antonio, Rauch, Anita, Boonsawat, Paranchai, Fagerberg, Christina R., Larsen, Martin J., Kibaek, Maria, Labalme, Audrey, Poisson, Alice, Payne, Katelyn K., Walsh, Laurence E., Aldinger, Kimberly A., Balciuniene, Jorune, Skraban, Cara, Gray, Christopher, Murrell, Jill, Bupp, Caleb P., Pascolini, Giulia, Grammatico, Paola, Broly, Martin, Küry, Sébastien, Nizon, Mathilde, Rasool, Iqra Ghulam, Zahoor, Muhammad Yasir, Kraus, Cornelia, Reis, André, Iqbal, Muhammad, Uguen, Kevin, Audebert-Bellanger, Severine, Ferec, Claude, Redon, Sylvia, Baker, Janice, Wu, Yunhong, Zampino, Guiseppe, Syrbe, Steffan, Brosse, Ines, Jamra, Rami Abou, Dobyns, William B., Cohen, Lilian L., Blomhoff, Anne, Mignot, Cyril, Keren, Boris, Courtin, Thomas, Agrawal, Pankaj B., Beggs, Alan H., and Yu, Timothy W.
Published: 2021
Full Text: View/download PDF

13. Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy

Author: Voisin, Norine, Schnur, Rhonda E., Douzgou, Sofia, Hiatt, Susan M., Rustad, Cecilie F., Brown, Natasha J., Earl, Dawn L., Keren, Boris, Levchenko, Olga, Geuer, Sinje, Verheyen, Sarah, Johnson, Diana, Zarate, Yuri A., Hančárová, Miroslava, Amor, David J., Bebin, E. Martina, Blatterer, Jasmin, Brusco, Alfredo, Cappuccio, Gerarda, Charrow, Joel, Chatron, Nicolas, Cooper, Gregory M., Courtin, Thomas, Dadali, Elena, Delafontaine, Julien, Del Giudice, Ennio, Doco, Martine, Douglas, Ganka, Eisenkölbl, Astrid, Funari, Tara, Giannuzzi, Giuliana, Gruber-Sedlmayr, Ursula, Guex, Nicolas, Heron, Delphine, Holla, Øystein L., Hurst, Anna C.E., Juusola, Jane, Kronn, David, Lavrov, Alexander, Lee, Crystle, Lorrain, Séverine, Merckoll, Else, Mikhaleva, Anna, Norman, Jennifer, Pradervand, Sylvain, Prchalová, Darina, Rhodes, Lindsay, Sanders, Victoria R., Sedláček, Zdeněk, Seebacher, Heidelis A., Sellars, Elizabeth A., Sirchia, Fabio, Takenouchi, Toshiki, Tanaka, Akemi J., Taska-Tench, Heidi, Tønne, Elin, Tveten, Kristian, Vitiello, Giuseppina, Vlčková, Markéta, Uehara, Tomoko, Nava, Caroline, Yalcin, Binnaz, Kosaki, Kenjiro, Donnai, Dian, Mundlos, Stefan, Brunetti-Pierri, Nicola, Chung, Wendy K., and Reymond, Alexandre
Published: 2021
Full Text: View/download PDF

14. LSM7 variants involving key amino acids for LSM complex function cause a neurodevelopmental disorder with leukodystrophy and cerebellar atrophy

Author: Crespin, Matis, Siquier-Pernet, Karine, Marzin, Pauline, Bole-Feysot, Christine, Malan, Valérie, Nitschké, Patrick, Hully, Marie, Roux, Charles-Joris, Lemoine, Michel, Rio, Marlène, Boddaert, Nathalie, Courtin, Thomas, and Cantagrel, Vincent
Published: 2025
Full Text: View/download PDF

15. Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature

Author: Torti, Erin, Keren, Boris, Palmer, Elizabeth E., Zhu, Zehua, Afenjar, Alexandra, Anderson, Ilse. J., Andrews, Marisa V., Atkinson, Celia, Au, Margaret, Berry, Susan A., Bowling, Kevin M., Boyle, Jackie, Buratti, Julien, Cathey, Sara S., Charles, Perrine, Cogne, Benjamin, Courtin, Thomas, Escobar, Luis F., Finley, Sabra Ledare, Graham, John M., Jr., Grange, Dorothy K., Heron, Delphine, Hewson, Stacy, Hiatt, Susan M., Hibbs, Kathleen A., Jayakar, Parul, Kalsner, Louisa, Larcher, Lise, Lesca, Gaetan, Mark, Paul R., Miller, Kathryn, Nava, Caroline, Nizon, Mathilde, Pai, G. Shashidhar, Pappas, John, Parsons, Gretchen, Payne, Katelyn, Putoux, Audrey, Rabin, Rachel, Sabatier, Isabelle, Shinawi, Marwan, Shur, Natasha, Skinner, Steven A., Valence, Stephanie, Warren, Hannah, Whalen, Sandra, Crunk, Amy, Douglas, Ganka, Monaghan, Kristin G., Person, Richard E., Willaert, Rebecca, Solomon, Benjamin D., and Juusola, Jane
Published: 2019
Full Text: View/download PDF

16. PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum

Author: Johannesen, Katrine M., Gardella, Elena, Gjerulfsen, Cathrine E., Bayat, Allan, Rouhl, Rob P.W., Reijnders, Margot, Whalen, Sandra, Keren, Boris, Buratti, Julien, Courtin, Thomas, Wierenga, Klaas J., Isidor, Bertrand, Piton, Amélie, Faivre, Laurence, Garde, Aurore, Moutton, Sébastien, Tran-Mau-Them, Frédéric, Denommé-Pichon, Anne-Sophie, Coubes, Christine, Larson, Austin, Esser, Michael J., Appendino, Juan Pablo, Al-Hertani, Walla, Gamboni, Beatriz, Mampel, Alejandra, Mayorga, Lía, Orsini, Alessandro, Bonuccelli, Alice, Suppiej, Agnese, Van-Gils, Julien, Vogt, Julie, Damioli, Simona, Giordano, Lucio, Moortgat, Stephanie, Wirrell, Elaine, Hicks, Sarah, Kini, Usha, Noble, Nathan, Stewart, Helen, Asakar, Shailesh, Cohen, Julie S., Naidu, SakkuBai R., Collier, Ashley, Brilstra, Eva H., Li, Mindy H., Brew, Casey, Bigoni, Stefania, Ognibene, Davide, Ballardini, Elisa, Ruivenkamp, Claudia, Faggioli, Raffaella, Afenjar, Alexandra, Rodriguez, Diana, Bick, David, Segal, Devorah, Coman, David, Gunning, Boudewijn, Devinsky, Orrin, Demmer, Laurie A., Grebe, Theresa, Pruna, Dario, Cursio, Ida, Greenhalgh, Lynn, Graziano, Claudio, Singh, Rahul Raman, Cantalupo, Gaetano, Willems, Marjolaine, Yoganathan, Sangeetha, Góes, Fernanda, Leventer, Richard J., Colavito, Davide, Olivotto, Sara, Scelsa, Barbara, Andrade, Andrea V., Ratke, Kelly, Tokarz, Farha, Khan, Atiya S., Ormieres, Clothilde, Benko, William, Keough, Karen, Keros, Sotirios, Hussain, Shanawaz, Franques, Ashlea, Varsalone, Felicia, Grønborg, Sabine, Mignot, Cyril, Heron, Delphine, Nava, Caroline, Isapof, Arnaud, Borlot, Felippe, Whitney, Robyn, Ronan, Anne, Foulds, Nicola, Somorai, Marta, Brandsema, John, Helbig, Katherine L., Helbig, Ingo, Ortiz-González, Xilma R., Dubbs, Holly, Vitobello, Antonio, Anderson, Mel, Spadafore, Dominic, Hunt, David, Møller, Rikke S., and Rubboli, Guido
Published: 2021
Full Text: View/download PDF

17. The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways

Author: Marie-Hardy, Laura, primary, Courtin, Thomas, additional, Pascal-Moussellard, Hugues, additional, Zakine, Serge, additional, and Brice, Alexis, additional
Published: 2023
Full Text: View/download PDF

18. PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

Author: Fevga, Christina, Tesson, Christelle, Carreras Mascaro, Ana, Courtin, Thomas, Van Coller, Riaan, Sakka, Salma, Ferraro, Federico, Farhat, Nouha, Bardien, Soraya, Damak, Mariem, Carr, Jonathan, Ferrien, Melanie, Boumeester, Valerie, Hundscheid, Jasmijn, Grillenzoni, Nicola, Kessissoglou, Irini A., Kuipers, Demy J.S., Quadri, Marialuisa, Agid, Yves, Anheim, Mathieu, Borg, Michel, Brice, Alexis, Broussolle, Emmanuel, Corvol, Jean Christophe, Damier, Philippe, Defebvre, Luc, Dürr, Alexandra, Durif, Franck, Houeto, Jean Luc, Krack, Paul, Klebe, Stephan, Lesage, Suzanne, Lohmann, Ebba, Martinez, Maria, Mangone, Graziella, Mariani, Louise Laure, Pollak, Pierre, Rascol, Olivier, Tison, François, Tranchant, Christine, Verin, Marc, Viallet, François, Vidailhet, Marie, Emre, Murat, Hanagasi, Hasmet, Bilgic, Basar, Lu, Bedia Marangozog, Benmahdjoub, Mustapha, Arezki, Mohammed, Bouchetara, Sofiane A., Benhassine, Traki, Tazir, Meriem, Djebara, Mouna Ben, Gouider, Riadh, Romdhan, Sawssan Ben, Mhiri, Chokri, Bouhouche, Ahmed, Bonifati, Vincenzo, Mandemakers, Wim, Kievit, Anneke J.A., Boon, Agnita J.W., Ferreira, Joaquim J., Guedes, Leonor Correia, Hanagasi, Hasmet A., Tufekcioglu, Zeynep, Elibol, Bulent, Dog.u, Okan, Gultekin, Murat, Chien, Hsin F., Barbosa, Egberto, Jardim, Laura Bannach, Rieder, Carlos R.M., Chang, Hsiu Chen, Lu, Chin Song, Wu-Chou, Yah Huei, Yeh, Tu Hsueh, Lopiano, Leonardo, Tassorelli, Cristina, Pacchetti, Claudio, Comi, Cristoforo, Raudino, Francesco, Bertolasi, Laura, Tinazzi, Michele, Bonizzato, Alberto, Ferracci, Carlo, Marconi, Roberto, Guidi, Marco, Onofrj, Marco, Thomas, Astrid, Vanacore, Nicola, Meco, Giuseppe, Fabrizio, Edito, Fabbrini, Giovanni, Berardelli, Alfredo, Stocchi, Fabrizio, Vacca, Laura, Barone, Paolo, Picillo, Marina, De Michele, Giuseppe, Criscuolo, Chiara, De Mari, Michele, Dell'aquila, Claudia, Iliceto, Giovanni, Toni, Vincenzo, Trianni, Giorgio, Saddi, Valeria, Cossu, Gianni, Melis, Maurizio, Hassan, Bassem A., Breedveld, Guido J., Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Faculty of Health Sciences [Pretoria], University of Pretoria [South Africa], Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Stellenbosch University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Motivation, cerveau et comportement = Motivation, Brain and Behavior [ICM Paris] (MBB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Tesson, Christelle, Clinical Genetics, and Neurology
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, PTPA, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], PPP2R4, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, parkinsonism, PP2A
Abstract: The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T>G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C>A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.
Published: 2023
Full Text: View/download PDF

19. Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

Author: Vetro, Annalisa, primary, Pelorosso, Cristiana, additional, Balestrini, Simona, additional, Masi, Alessio, additional, Hambleton, Sophie, additional, Argilli, Emanuela, additional, Conti, Valerio, additional, Giubbolini, Simone, additional, Barrick, Rebekah, additional, Bergant, Gaber, additional, Writzl, Karin, additional, Bijlsma, Emilia K., additional, Brunet, Theresa, additional, Cacheiro, Pilar, additional, Mei, Davide, additional, Devlin, Anita, additional, Hoffer, Mariëtte J.V., additional, Machol, Keren, additional, Mannaioni, Guido, additional, Sakamoto, Masamune, additional, Menezes, Manoj P., additional, Courtin, Thomas, additional, Sherr, Elliott, additional, Parra, Riccardo, additional, Richardson, Ruth, additional, Roscioli, Tony, additional, Scala, Marcello, additional, von Stülpnagel, Celina, additional, Smedley, Damian, additional, Torella, Annalaura, additional, Tohyama, Jun, additional, Koichihara, Reiko, additional, Hamada, Keisuke, additional, Ogata, Kazuhiro, additional, Suzuki, Takashi, additional, Sugie, Atsushi, additional, van der Smagt, Jasper J., additional, van Gassen, Koen, additional, Valence, Stephanie, additional, Vittery, Emma, additional, Malone, Stephen, additional, Kato, Mitsuhiro, additional, Matsumoto, Naomichi, additional, Ratto, Gian Michele, additional, Guerrini, Renzo, additional, Pochiero, Francesca, additional, Mari, Francesco, additional, Ramesh, Venkateswaran, additional, Capra, Valeria, additional, Mancardi, Margherita, additional, Keren, Boris, additional, Mignot, Cyiril, additional, Lulli, Matteo, additional, Parks, Kendall, additional, Griffin, Helen, additional, Brugger, Melanie, additional, Nigro, Vincenzo, additional, Hirata, Yuko, additional, Peterlin, Borut, additional, Maki, Ryuto, additional, Nitta, Yohei, additional, Ambrose, John C., additional, Arumugam, Prabhu, additional, Bevers, Roel, additional, Bleda, Marta, additional, Boardman-Pretty, Freya, additional, Boustred, Christopher R., additional, Brittain, Helen, additional, Brown, Matthew A., additional, Caulfield, Mark J., additional, Chan, Georgia C., additional, Giess, Adam, additional, Griffin, John N., additional, Hamblin, Angela, additional, Henderson, Shirley, additional, Hubbard, Tim J.P., additional, Jackson, Rob, additional, Jones, Louise J., additional, Kasperaviciute, Dalia, additional, Kayikci, Melis, additional, Kousathanas, Athanasios, additional, Lahnstein, Lea, additional, Lakey, Anna, additional, Leigh, Sarah E.A., additional, Leong, Ivonne U.S., additional, Lopez, Javier F., additional, Maleady-Crowe, Fiona, additional, McEntagart, Meriel, additional, Minneci, Federico, additional, Mitchell, Jonathan, additional, Moutsianas, Loukas, additional, Mueller, Michael, additional, Murugaesu, Nirupa, additional, Need, Anna C., additional, O’Donovan, Peter, additional, Odhams, Chris A., additional, Patch, Christine, additional, Perez-Gil, Daniel, additional, Pereira, Marina B., additional, Pullinger, John, additional, Rahim, Tahrima, additional, Rendon, Augusto, additional, Rogers, Tim, additional, Savage, Kevin, additional, Sawant, Kushmita, additional, Scott, Richard H., additional, Siddiq, Afshan, additional, Sieghart, Alexander, additional, Smith, Samuel C., additional, Sosinsky, Alona, additional, Stuckey, Alexander, additional, Tanguy, Mélanie, additional, Taylor Tavares, Ana Lisa, additional, Thomas, Ellen R.A., additional, Thompson, Simon R., additional, Tucci, Arianna, additional, Welland, Matthew J., additional, Williams, Eleanor, additional, Witkowska, Katarzyna, additional, Wood, Suzanne M., additional, and Zarowiecki, Magdalena, additional
Published: 2023
Full Text: View/download PDF

20. Loss-of-function variants inCUL3cause a syndromic neurodevelopmental disorder

Author: Blackburn, Patrick R., primary, Ebstein, Frédéric, additional, Hsieh, Tzung-Chien, additional, Motta, Marialetizia, additional, Radio, Francesca Clementina, additional, Herkert, Johanna C., additional, Rinne, Tuula, additional, Thiffault, Isabelle, additional, Rapp, Michele, additional, Alders, Mariel, additional, Maas, Saskia, additional, Gerard, Bénédicte, additional, Smol, Thomas, additional, Vincent-Delorme, Catherine, additional, Cogné, Benjamin, additional, Isidor, Bertrand, additional, Vincent, Marie, additional, Bachmann-Gagescu, Ruxandra, additional, Rauch, Anita, additional, Joset, Pascal, additional, Ferrero, Giovanni Battista, additional, Ciolfi, Andrea, additional, Husson, Thomas, additional, Guerrot, Anne-Marie, additional, Bacino, Carlos, additional, Macmurdo, Colleen, additional, Thompson, Stephanie S., additional, Rosenfeld, Jill A., additional, Faivre, Laurence, additional, Mau-Them, Frederic Tran, additional, Deb, Wallid, additional, Vignard, Virginie, additional, Agrawal, Pankaj B., additional, Madden, Jill A., additional, Goldenberg, Alice, additional, Lecoquierre, François, additional, Zech, Michael, additional, Prokisch, Holger, additional, Necpál, Ján, additional, Jech, Robert, additional, Winkelmann, Juliane, additional, Koprušáková, Monika Turčanová, additional, Konstantopoulou, Vassiliki, additional, Younce, John R., additional, Shinawi, Marwan, additional, Mighton, Chloe, additional, Fung, Charlotte, additional, Morel, Chantal, additional, Ellis, Jordan Lerner-, additional, DiTroia, Stephanie, additional, Barth, Magalie, additional, Bonneau, Dominique, additional, Krapels, Ingrid, additional, Stegmann, Sander, additional, Schoot, Vyne van der, additional, Brunet, Theresa, additional, Bußmann, Cornelia, additional, Mignot, Cyril, additional, Courtin, Thomas, additional, Ravelli, Claudia, additional, Keren, Boris, additional, Ziegler, Alban, additional, Hasadsri, Linda, additional, Pichurin, Pavel N., additional, Klee, Eric W., additional, Grand, Katheryn, additional, Sanchez-Lara, Pedro A., additional, Krüger, Elke, additional, Bézieau, Stéphane, additional, Klinkhammer, Hannah, additional, Krawitz, Peter Michael, additional, Eichler, Evan E., additional, Tartaglia, Marco, additional, Küry, Sébastien, additional, and Wang, Tianyun, additional
Published: 2023
Full Text: View/download PDF

21. P428: De novo truncating variants in ZNF865: A putative cause of a neurodevelopmental disorder

Author: Bradbrook, Sam, Graham, Gail, Carter, Melissa, Kibaek, Maria, Larsen, Martin, Fagerberg, Christina, Dawson, Katherine, Meuter, Cheryl, Pepler, Alexander, Besnard, Thomas, Isidor, Bertrand, Bezieau, Stéphane, Cogné, Benjamin, Vincent, Marie, Bjorgo, Katherine, Courtin, Thomas, Emrick, Lisa, Rosenfeld, Jill, Network, Undiagnosed Diseases, Martinez-Agosto, Julian, Heulin, Mathilde, Morin, Gilles, Monin, Pauline, Januel, Louis, Bonnet-Dupeyron, Marie-Noëlle, Pujalte, Mathilde, Worley, Kim, Weisz-Hubshman, Monika, Dickson, Patricia, Thompson, Michelle, and Marcadier, Julien
Published: 2024
Full Text: View/download PDF

22. Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder

Author: Blackburn, Patrick R., Ebstein, Frédéric, Hsieh, Tzung-Chien, Motta, Marialetizia, Radio, Francesca Clementina, Herkert, Johanna C., Rinne, Tuula, Thiffault, Isabelle, Rapp, Michele, Alders, Mariel, Maas, Saskia, Gerard, Bénédicte, Smol, Thomas, Vincent-Delorme, Catherine, Cogné, Benjamin, Isidor, Bertrand, Vincent, Marie, Bachmann-Gagescu, Ruxandra, Rauch, Anita, Joset, Pascal, Ferrero, Giovanni Battista, Ciolfi, Andrea, Husson, Thomas, Guerrot, Anne-Marie, Bacino, Carlos, Macmurdo, Colleen, Thompson, Stephanie S., Rosenfeld, Jill A., Faivre, Laurence, Mau-Them, Frederic Tran, Deb, Wallid, Vignard, Virginie, Agrawal, Pankaj B., Madden, Jill A., Goldenberg, Alice, Lecoquierre, François, Zech, Michael, Prokisch, Holger, Necpál, Ján, Jech, Robert, Winkelmann, Juliane, Koprušáková, Monika Turčanová, Konstantopoulou, Vassiliki, Younce, John R., Shinawi, Marwan, Mighton, Chloe, Fung, Charlotte, Morel, Chantal, Ellis, Jordan Lerner, DiTroia, Stephanie, Barth, Magalie, Bonneau, Dominique, Krapels, Ingrid, Stegmann, Sander, van der Schoot, Vyne, Brunet, Theresa, Bußmann, Cornelia, Mignot, Cyril, Courtin, Thomas, Ravelli, Claudia, Keren, Boris, Ziegler, Alban, Hasadsri, Linda, Pichurin, Pavel N., Klee, Eric W., Grand, Katheryn, Sanchez-Lara, Pedro A., Krüger, Elke, Bézieau, Stéphane, Klinkhammer, Hannah, Krawitz, Peter Michael, Eichler, Evan E., Tartaglia, Marco, Küry, Sébastien, and Wang, Tianyun
Subjects: Article
Abstract: PURPOSE: De novo variants in CUL3 (Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism. METHODS: Genetic data and detailed clinical records were collected via multi-center collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells. RESULTS: We assembled a cohort of 35 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugates in vitro . Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells. CONCLUSION: Our study further refines the clinical and mutational spectrum of CUL3 -associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism.
Published: 2023

23. Genotype-Phenotype correlation in Parkin-Parkinson’s disease (P3-11.012)

Author: Menon, Poornima Jayadev, primary, Sambin, Sara, additional, Criniere-Boizet, Baptiste, additional, Courtin, Thomas, additional, Casse, Fanny, additional, Tesson, Christelle, additional, Ferrien, Melanie, additional, Flamand-Roze, Emmanuel, additional, Lejeune, Francois-Xavier, additional, Lanore, Aymeric, additional, Mangone, Graziella, additional, Mariani, Louise-Laure, additional, Aasly, Jan, additional, Or, Ziv Gan, additional, Yu, Eric, additional, Dauvilliers, Yves, additional, Zimprich, Alexander, additional, Fernandez, Ignacio Alvarez, additional, Pastor, Pau, additional, Di Fonzo, Alessio, additional, Bhatia, Khailash, additional, Magrinelli, Francesca, additional, Houlden, Henry, additional, Real, Raquel, additional, Narendra, Derek, additional, Lin, Hsin-Pin, additional, Jovanovic, Carna, additional, Koks, Sulev, additional, Lynch, Timothy, additional, Gallagher, Amy, additional, Vandenberghe, Wim, additional, Gasser, Thomas, additional, Morris, Huw, additional, Klein, Christine, additional, Brockmann, Kathrin, additional, Corti, Olga, additional, Brice, Alexis, additional, Lesage, Suzanne, additional, and Corvol, Jean-Christophe, additional
Published: 2023
Full Text: View/download PDF

24. Differences in Survival across Monogenic Forms of Parkinson's Disease.

Author: Lanore, Aymeric, Casse, Fanny, Tesson, Christelle, Courtin, Thomas, Menon, Poornima Jayadev, Sambin, Sara, Mangone, Graziella, Mariani, Louise‐Laure, Lesage, Suzanne, Brice, Alexis, Elbaz, Alexis, Corvol, Jean‐Christophe, Agid, Yves, Anheim, Mathieu, Borg, Michel, Broussolle, Emmanuel, Damier, Philippe, Defebvre, Luc, Dürr, Alexandra, and Durif, Franck
Subjects: PARKINSON'S disease, GENETIC counseling, DARDARIN, OVERALL survival, VITAL records (Births, deaths, etc.), MOVEMENT disorders
Abstract: Objective: Survival of patients with monogenic Parkinson's disease may depend on the causative genes associated with the disease. In this study, we compare survival of patients with Parkinson's disease according to the presence of SNCA, PRKN, LRRK2, or GBA mutations. Methods: Data from the French Parkinson Disease Genetics national multicenter cohort study were used. Patients with sporadic and familial Parkinson's disease were recruited between 1990 and 2021. Patients were genotyped for the presence of mutations in the SNCA, PRKN, LRRK2, or GBA genes. Vital status was collected from the National death register for participants born in France. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariable Cox proportional hazards regression. Results: Of the 2,037 patients with Parkinson's disease, 889 had died after a follow‐up of up to 30 years. Patients with PRKN (n = 100, HR = 0.41; p = 0.001) and LRRK2 mutations (n = 51, HR = 0.49; p = 0.023) had longer survival than those without any mutation, whereas patients with SNCA (n = 20, HR = 9.88; p < 0.001) or GBA mutations (n = 173, HR = 1.33; p = 0.048) had shorter survival. Interpretation: Survival differs across genetic forms of Parkinson's disease, with higher mortality for patients with SNCA or GBA mutations, and lower mortality for those with PRKN or LRRK2 mutations. Differences in severity and disease progression among monogenic forms of Parkinson's disease likely explain these findings, which has important consequences for genetic counselling and choice of end points for future clinical trials for targeted therapies. ANN NEUROL 2023;94:123–132 [ABSTRACT FROM AUTHOR]
Published: 2023
Full Text: View/download PDF

25. Heterozygous variants in CTR9, which encodes a major component of the PAF1 complex, are associated with a neurodevelopmental disorder

Author: Meuwissen, Marije, Verstraeten, Aline, Ranza, Emmanuelle, Iwaszkiewicz, Justyna, Bastiaansen, Maaike, Mateiu, Ligia, Nemegeer, Merlijn, Meester, Josephina A.N., Afenjar, Alexandra, Amaral, Michelle, Ballhausen, Diana, Barnett, Sarah, Barth, Magalie, Asselbergh, Bob, Spaas, Katrien, Heeman, Bavo, Bassetti, Jennifer, Blackburn, Patrick, Schaer, Marie, Blanc, Xavier, Zoete, Vincent, Casas, Kari, Courtin, Thomas, Doummar, Diane, Guerry, Frédéric, Keren, Boris, Pappas, John, Rabin, Rachel, Begtrup, Amber, Shinawi, Marwan, Vulto-van Silfhout, Anneke T., Kleefstra, Tjitske, Wagner, Matias, Ziegler, Alban, Schaefer, Elise, Gerard, Benedicte, De Bie, Charlotte I., Holwerda, Sjoerd J.B., Abbot, Mary Alice, Antonarakis, Stylianos E., and Loeys, Bart
Published: 2022
Full Text: View/download PDF

26. Polymicrogyria with Dysmorphic Neurons in a Patient with SCN2A Mutation

Author: Gelot, Antoinette-Bernabe, primary, Courtin, Thomas, additional, Sileo, Chiara, additional, Keren, Boris, additional, Soreze-Smagghue, Yohan, additional, Whalen, Sandra, additional, and Represa, Alfonso, additional
Published: 2022
Full Text: View/download PDF

27. TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia

Author: Tábara, Luis Carlos, primary, Al-Salmi, Fatema, additional, Maroofian, Reza, additional, Al-Futaisi, Amna Mohammed, additional, Al-Murshedi, Fathiya, additional, Kennedy, Joanna, additional, Day, Jacob O, additional, Courtin, Thomas, additional, Al-Khayat, Aisha, additional, Galedari, Hamid, additional, Mazaheri, Neda, additional, Protasoni, Margherita, additional, Johnson, Mark, additional, Leslie, Joseph S, additional, Salter, Claire G, additional, Rawlins, Lettie E, additional, Fasham, James, additional, Al-Maawali, Almundher, additional, Voutsina, Nikol, additional, Charles, Perrine, additional, Harrold, Laura, additional, Keren, Boris, additional, Kunji, Edmund R S, additional, Vona, Barbara, additional, Jelodar, Gholamreza, additional, Sedaghat, Alireza, additional, Shariati, Gholamreza, additional, Houlden, Henry, additional, Crosby, Andrew H, additional, Prudent, Julien, additional, and Baple, Emma L, additional
Published: 2022
Full Text: View/download PDF

28. Understanding the new BRD4‐related syndrome: Clinical and genomic delineation with an international cohort study

Author: Jouret, Guillaume, primary, Heide, Solveig, additional, Sorlin, Arthur, additional, Faivre, Laurence, additional, Chantot‐Bastaraud, Sandra, additional, Beneteau, Claire, additional, Denis‐Musquer, Marie, additional, Turnpenny, Peter D., additional, Coutton, Charles, additional, Vieville, Gaëlle, additional, Thevenon, Julien, additional, Larson, Austin, additional, Petit, Florence, additional, Boudry, Elise, additional, Smol, Thomas, additional, Delobel, Bruno, additional, Duban‐Bedu, Bénédicte, additional, Fallerini, Chiara, additional, Mari, Francesca, additional, Lo Rizzo, Caterina, additional, Renieri, Alessandra, additional, Caberg, Jean‐Hubert, additional, Denommé‐Pichon, Anne‐Sophie, additional, Tran Mau‐Them, Frédéric, additional, Maystadt, Isabelle, additional, Courtin, Thomas, additional, Keren, Boris, additional, Mouthon, Linda, additional, Charles, Perrine, additional, Cuinat, Silvestre, additional, Isidor, Bertrand, additional, Theis, Philippe, additional, Müller, Christian, additional, Kulisic, Marizela, additional, Türkmen, Seval, additional, Stieber, Daniel, additional, Bourgeois, Dominique, additional, Scalais, Emmanuel, additional, and Klink, Barbara, additional
Published: 2022
Full Text: View/download PDF

29. Additional file 5 of Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Abstract: Additional file 5: Table S2. Seizure and seizure-like episodes in affected individuals with at least one afebrile seizure.
Published: 2022
Full Text: View/download PDF

30. Additional file 6 of Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Abstract: Additional file 6: Figure S1. TASK3 conformational changes define PC motions and channel gating. Figure S2. Detailed view of the TASK3 selectivity filter and surrounding residues. Figure S3. Distributions of K+ ions for selected positions along the transport process, and across variants. Figure S4. Genomic variants lead to changes in K+ concentration at the selectivity filter. Figure S5. Cellular localization of labelled TASK3 variants. Figure S6. Comparison of whole cell current density for Tyr205Cys in the presence of various cysteine-modifying agents.
Published: 2022
Full Text: View/download PDF

31. Additional file 1 of Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Abstract: Additional file 1: Supplementary Note. Clinical Histories. Written clinical histories including genetic testing for each novel family in this study. Molecular Modeling Reveals Mutation-Specific Effects on Channel Mechanics. Molecular Dynamics Simulations Show Changes in Potassium Ion Distribution.
Published: 2022
Full Text: View/download PDF

32. Temporal trends in mercury concentrations in eggs of Tawny owl (Strix aluco) from Central Norway between 1986-2019: influence of dietary ecological parameters and climate variables

Author: Courtin, Thomas Victor Robert, Bourgeon, Sophie, Bustnes, Jan Ove, Eulaers, Igor, and Hansen, Elisabeth
Subjects: Climate variable, Temporal trends, Mercury, Stable isotope, Tawny owl
Abstract: Mercury (Hg) is considered as a global threat which is emitted in the environment through natural sources or anthropogenic activities. Emissions of mercury decreased during the last decades because of the implementation of mitigation measures. However, with the ongoing climate change, ecosystems are directly (e.g., rising temperature) or indirectly impacted (i.e., altered ecosystem by e.g., invasive species and over-harvesting). Therefore, climate variables should be integrated in assessing pollutant temporal trends. In the current study, we investigated the temporal trends of Hg concentrations over a 33-year period (1986-2019). The potential influence of climate variables (i.e., air temperature, maximum snow depth, and the North Atlantic Oscillation) and dietary ecological parameters (i.e., carbon and nitrogen stable isotopes, ∂13C and ∂15N) on the Hg concentrations in tawny owl eggs were also investigated. Mercury and stable isotope values were analyzed in eggs and the data for the air temperature and the maximum snow depth for the winter period (December-March) were retrieved from several stations surrounding Trondheim. The average values for the three climate variables (i.e., temperature, max snow depth, and North Atlantic Oscillation (NAO)) were calculated for the entire winter period (December-March). A sudden shift in Hg concentrations was observed between 2000 and 2005 while exploring the dataset, two periods (1986-2005 and 2006-2019) were therefore investigated. A significant difference (p < 0.01) was observed between the two periods (0.12 ± 0.07 μg.g-1 and 0.074 ± 0.039 μg.g-1, respectively). A significant annual decrease of 0.002 μg.g-1 in mercury concentration was observed throughout the entire studied period (t = -5.42, p < 0.001). Among the different models selected to investigate the influence of dietary ecology and the climate variables on temporal trends of Hg, the most parsimonious model included the influence of the temperature and the ∂13C. Therefore, temperature and feeding habitat (∂13C) were found to have a higher influence on egg Hg than trophic level (∂15N), precipitations (snow), and larger scale climate variable (NAO).
Published: 2022

33. Additional file 9 of Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Abstract: Additional file 9: Table S5. A comparison of GPCRs regulation between TASK3 clinical variants and WT controls.
Published: 2022
Full Text: View/download PDF

34. Additional file 7 of Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Abstract: Additional file 7: Table S3. A comparison of whole cell current density and reversal potentials between TASK3 clinical variants and matched WT controls.
Published: 2022
Full Text: View/download PDF

35. Additional file 8 of Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Author: Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
Abstract: Additional file 8: Table S4. A comparison of inhibition by extracellular acidification (pH 6.4) between TASK3 clinical variants and WT controls.
Published: 2022
Full Text: View/download PDF

36. Detection of ATXN2 Expansions in an Exome Dataset: An Underdiagnosed Cause of Parkinsonism.

Author: Casse, Fanny, Courtin, Thomas, Tesson, Christelle, Ferrien, Mélanie, Noël, Sandrine, Fauret‐Amsellem, Anne‐Laure, Gareau, Thomas, Guegan, Justine, Anheim, Mathieu, Mariani, Louise‐Laure, Le Forestier, Nadine, Tranchant, Christine, Corvol, Jean‐Christophe, Lesage, Suzanne, and Brice, Alexis
Subjects: *PARKINSON'S disease, *PARKINSONIAN disorders, *SPINOCEREBELLAR ataxia, *POLYMERASE chain reaction
Abstract: Background: CAG‐repeat expansions in Ataxin 2 (ATXN2) are known to cause spinocerebellar ataxia type 2 (SCA2), but CAA interrupted expansions may also result in autosomal dominant Parkinson's disease (AD PD). However, because of technical limitations, such expansions are not explored in whole exome sequencing (WES) data. Objectives: To identify ATXN2 expansions using WES data from PD cases. Methods: We explored WES data from a cohort of 477 index cases with PD using ExpansionHunter (Illumina DRAGEN Bio‐IT Platform, San Diego, CA). Putative expansions were confirmed by combining polymerase chain reaction and fragment length analysis followed by sub‐cloning and sequencing methods. Results: Using ExpansionHunter, we identified three patients from two families with AD PD carrying either ATXN2 22/39 or 22/37 repeats, both interrupted by four CAA repeats. Conclusion: These findings demonstrate the usefulness of WES to detect pathogenic CAG repeat expansions, which were found in 1.7% of AD PD in the ATXN2 gene in our exome dataset. [ABSTRACT FROM AUTHOR]
Published: 2023
Full Text: View/download PDF

37. The commercial genetic testing landscape for Parkinson's disease

Author: Brice, Alexis, Kumeh, Amasi, West, Andrew B., Singleton, Andrew, Naito, Anna, Schüle, Birgitt, Fiske, Brian, Gabbert, Carolin, Klein, Christine, Marras, Connie, Blauwendraat, Cornelis, Thaxton, Courtney, Alessi, Dario, Craig, David, Fon, Edward A., Forbes, Emily, Valente, Enza Maria, Sammler, Esther, Chao, Gill, Riboldi, Giulietta, Elloumi, Houda Zghal, Mata, Ignacio, Beck, James C., Fong, Jamie C., Corvol, Jean-Christophe, Schulze, Jeanine, Verbrugge, Jennifer, Shulman, Joshua, Peterschmitt, Judith, Marder, Karen, Lohmann, Katja, Nudelman, Kelly, Lange, Lara, Cook, Lola, Cookson, Mark R., Nance, Martha, Farrer, Matthew, Grigorian, Melina, Schwarzschild, Michael A., Mencacci, Niccolo, Ross, Owen, Mistry, Pramod, Hodges, Priscila, Blake, Rachel, Saunders-Pullman, Rachel, Alcalay, Roy N., Sardi, S. Pablo, Farhan, Sali, Strom, Samuel, Padmanabhan, Shalini, Mohan, Shruthi, Longerich, Simonne, Schneider, Susanne, Lesage, Suzanne, Bardakjian, Tanya, Foroud, Tatiana, Courtin, Thomas, Tropea, Thomas, Liu, Yunlong, Gan-Or, Ziv, Shalash, Ali S., Hall, Anne, Thaler, Avner, Sue, Carolyn M., Mascalzoni, Deborah, Raymond, Deborah, Gatto, Emilia Mabel, Pal, Gian D., König, Inke, Novakovic, Ivana, Merello, Marcelo, Salari, Mehri, Mencacci, Niccolo Emanuele, Hattori, Nobutaka, Suchowersky, Oksana, Bardien, Soraya, Chung, Sun Ju, Simuni, Tatyana, Lynch, Timothy, Bonifati, Vincenzo, and Marder, Karen S.
Published: 2021
Full Text: View/download PDF

38. The commercial genetic testing landscape for Parkinson's disease

Author: Cook, Lola, primary, Schulze, Jeanine, additional, Verbrugge, Jennifer, additional, Beck, James C., additional, Marder, Karen S., additional, Saunders-Pullman, Rachel, additional, Klein, Christine, additional, Naito, Anna, additional, Alcalay, Roy N., additional, Brice, Alexis, additional, Kumeh, Amasi, additional, West, Andrew B., additional, Singleton, Andrew, additional, Schüle, Birgitt, additional, Fiske, Brian, additional, Gabbert, Carolin, additional, Marras, Connie, additional, Blauwendraat, Cornelis, additional, Thaxton, Courtney, additional, Alessi, Dario, additional, Craig, David, additional, Fon, Edward A., additional, Forbes, Emily, additional, Valente, Enza Maria, additional, Sammler, Esther, additional, Chao, Gill, additional, Riboldi, Giulietta, additional, Elloumi, Houda Zghal, additional, Mata, Ignacio, additional, Fong, Jamie C., additional, Corvol, Jean-Christophe, additional, Shulman, Joshua, additional, Peterschmitt, Judith, additional, Marder, Karen, additional, Lohmann, Katja, additional, Nudelman, Kelly, additional, Lange, Lara, additional, Cook, Lola, additional, Cookson, Mark R., additional, Nance, Martha, additional, Farrer, Matthew, additional, Grigorian, Melina, additional, Schwarzschild, Michael A., additional, Mencacci, Niccolo, additional, Ross, Owen, additional, Mistry, Pramod, additional, Hodges, Priscila, additional, Blake, Rachel, additional, Sardi, S. Pablo, additional, Farhan, Sali, additional, Strom, Samuel, additional, Padmanabhan, Shalini, additional, Mohan, Shruthi, additional, Longerich, Simonne, additional, Schneider, Susanne, additional, Lesage, Suzanne, additional, Bardakjian, Tanya, additional, Foroud, Tatiana, additional, Courtin, Thomas, additional, Tropea, Thomas, additional, Liu, Yunlong, additional, Gan-Or, Ziv, additional, Shalash, Ali S., additional, Hall, Anne, additional, Thaler, Avner, additional, Sue, Carolyn M., additional, Mascalzoni, Deborah, additional, Raymond, Deborah, additional, Gatto, Emilia Mabel, additional, Pal, Gian D., additional, König, Inke, additional, Novakovic, Ivana, additional, Merello, Marcelo, additional, Salari, Mehri, additional, Mencacci, Niccolo Emanuele, additional, Hattori, Nobutaka, additional, Suchowersky, Oksana, additional, Bardien, Soraya, additional, Chung, Sun Ju, additional, Simuni, Tatyana, additional, Lynch, Timothy, additional, and Bonifati, Vincenzo, additional
Published: 2021
Full Text: View/download PDF

39. Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

Author: Chopra, Maya, McEntagart, Meriel, Clayton-Smith, Jill, Platzer, Konrad, Shukla, Anju, Girisha, Katta M., Kaur, Anupriya, Kaur, Parneet, Pfundt, Rolph, Veenstra-Knol, Hermine, Mancini, Grazia M.S., Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Kortüm, Fanny, Hempel, Maja, Denecke, Jonas, Lehman, Anna, Kleefstra, Tjitske, Stuurman, Kyra E., Wilke, Martina, Thompson, Michelle L., Bebin, E. Martina, Bijlsma, Emilia K., Hoffer, Mariette J.V., Peeters-Scholte, Cacha, Slavotinek, Anne, Weiss, William A., Yip, Tiffany, Hodoglugil, Ugur, Whittle, Amy, diMonda, Janette, Neira, Juanita, Yang, Sandra, Kirby, Amelia, Pinz, Hailey, Lechner, Rosan, Sleutels, Frank, Helbig, Ingo, McKeown, Sarah, Helbig, Katherine, Willaert, Rebecca, Juusola, Jane, Semotok, Jennifer, Hadonou, Medard, Short, John, Yachelevich, Naomi, Lala, Sajel, Fernández-Jaen, Alberto, Pelayo, Janvier Porta, Klöckner, Chiara, Kamphausen, Susanne B., Abou Jamra, Rami, Arelin, Maria, Innes, A. Micheil, Niskakoski, Anni, Amin, Sam, Williams, Maggie, Evans, Julie, Smithson, Sarah, Smedley, Damian, de Burca, Anna, Kini, Usha, Delatycki, Martin B., Gallacher, Lyndon, Yeung, Alison, Pais, Lynn, Field, Michael, Martin, Ellenore, Charles, Perrine, Courtin, Thomas, Keren, Boris, Iascone, Maria, Cereda, Anna, Poke, Gemma, Abadie, Véronique, Chalouhi, Christel, Parthasarathy, Padmini, Halliday, Benjamin J., Robertson, Stephen P., Lyonnet, Stanislas, Amiel, Jeanne, and Gordon, Christopher T.
Published: 2021
Full Text: View/download PDF

40. Delineating the genotypic and phenotypic spectrum of HECW2-related neurodevelopmental disorders

Author: Acharya, Anushree, primary, Kavus, Haluk, additional, Dunn, Patrick, additional, Nasir, Abdul, additional, Folk, Leandra, additional, Withrow, Kara, additional, Wentzensen, Ingrid M., additional, Ruzhnikov, Maura R. Z., additional, Fallot, Camille, additional, Smol, Thomas, additional, Rama, Mélanie, additional, Brown, Kathleen, additional, Whalen, Sandra, additional, Ziegler, Alban, additional, Barth, Magali, additional, Chassevent, Anna, additional, Smith-Hicks, Constance, additional, Afenjar, Alexandra, additional, Courtin, Thomas, additional, Heide, Solveig, additional, Font-Montgomery, Esperanza, additional, Heid, Caleb, additional, Hamm, J. Austin, additional, Love, Donald R., additional, Thabet, Farouq, additional, Misra, Vinod K., additional, Cunningham, Mitch, additional, Leal, Suzanne M., additional, Jarvela, Irma, additional, Normand, Elizabeth A., additional, Zou, Fanggeng, additional, Helal, Mayada, additional, Keren, Boris, additional, Torti, Erin, additional, Chung, Wendy K., additional, and Schrauwen, Isabelle, additional
Published: 2021
Full Text: View/download PDF

41. Monogenic PD in Brazil: a step towards precision medicine

Author: Courtin, Thomas, primary and Brice, Alexis, additional
Published: 2021
Full Text: View/download PDF

42. Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Author: Genetica Klinische Genetica, Child Health, Genetica Sectie Genoomdiagnostiek, Harris, Holly K, Nakayama, Tojo, Lai, Jenny, Zhao, Boxun, Argyrou, Nikoleta, Gubbels, Cynthia S, Soucy, Aubrie, Genetti, Casie A, Suslovitch, Victoria, Rodan, Lance H, Tiller, George E, Lesca, Gaetan, Gripp, Karen W, Asadollahi, Reza, Hamosh, Ada, Applegate, Carolyn D, Turnpenny, Peter D, Simon, Marleen E H, Volker-Touw, Catharina M L, Gassen, Koen L I van, Binsbergen, Ellen van, Pfundt, Rolph, Gardeitchik, Thatjana, Vries, Bert B A de, Immken, LaDonna L, Buchanan, Catherine, Willing, Marcia, Toler, Tomi L, Fassi, Emily, Baker, Laura, Vansenne, Fleur, Wang, Xiadong, Ambrus, Julian L, Fannemel, Madeleine, Posey, Jennifer E, Agolini, Emanuele, Novelli, Antonio, Rauch, Anita, Boonsawat, Paranchai, Fagerberg, Christina R, Larsen, Martin J, Kibaek, Maria, Labalme, Audrey, Poisson, Alice, Payne, Katelyn K, Walsh, Laurence E, Aldinger, Kimberly A, Balciuniene, Jorune, Skraban, Cara, Gray, Christopher, Murrell, Jill, Bupp, Caleb P, Pascolini, Giulia, Grammatico, Paola, Broly, Martin, Küry, Sébastien, Nizon, Mathilde, Rasool, Iqra Ghulam, Zahoor, Muhammad Yasir, Kraus, Cornelia, Reis, André, Iqbal, Muhammad, Uguen, Kevin, Audebert-Bellanger, Severine, Ferec, Claude, Redon, Sylvia, Baker, Janice, Wu, Yunhong, Zampino, Guiseppe, Syrbe, Steffan, Brosse, Ines, Jamra, Rami Abou, Dobyns, William B, Cohen, Lilian L, Blomhoff, Anne, Mignot, Cyril, Keren, Boris, Courtin, Thomas, Agrawal, Pankaj B, Beggs, Alan H, Yu, Timothy W, Genetica Klinische Genetica, Child Health, Genetica Sectie Genoomdiagnostiek, Harris, Holly K, Nakayama, Tojo, Lai, Jenny, Zhao, Boxun, Argyrou, Nikoleta, Gubbels, Cynthia S, Soucy, Aubrie, Genetti, Casie A, Suslovitch, Victoria, Rodan, Lance H, Tiller, George E, Lesca, Gaetan, Gripp, Karen W, Asadollahi, Reza, Hamosh, Ada, Applegate, Carolyn D, Turnpenny, Peter D, Simon, Marleen E H, Volker-Touw, Catharina M L, Gassen, Koen L I van, Binsbergen, Ellen van, Pfundt, Rolph, Gardeitchik, Thatjana, Vries, Bert B A de, Immken, LaDonna L, Buchanan, Catherine, Willing, Marcia, Toler, Tomi L, Fassi, Emily, Baker, Laura, Vansenne, Fleur, Wang, Xiadong, Ambrus, Julian L, Fannemel, Madeleine, Posey, Jennifer E, Agolini, Emanuele, Novelli, Antonio, Rauch, Anita, Boonsawat, Paranchai, Fagerberg, Christina R, Larsen, Martin J, Kibaek, Maria, Labalme, Audrey, Poisson, Alice, Payne, Katelyn K, Walsh, Laurence E, Aldinger, Kimberly A, Balciuniene, Jorune, Skraban, Cara, Gray, Christopher, Murrell, Jill, Bupp, Caleb P, Pascolini, Giulia, Grammatico, Paola, Broly, Martin, Küry, Sébastien, Nizon, Mathilde, Rasool, Iqra Ghulam, Zahoor, Muhammad Yasir, Kraus, Cornelia, Reis, André, Iqbal, Muhammad, Uguen, Kevin, Audebert-Bellanger, Severine, Ferec, Claude, Redon, Sylvia, Baker, Janice, Wu, Yunhong, Zampino, Guiseppe, Syrbe, Steffan, Brosse, Ines, Jamra, Rami Abou, Dobyns, William B, Cohen, Lilian L, Blomhoff, Anne, Mignot, Cyril, Keren, Boris, Courtin, Thomas, Agrawal, Pankaj B, Beggs, Alan H, and Yu, Timothy W
Published: 2021

43. Delineating the genotypic and phenotypic spectrum of HECW2-related neurodevelopmental disorders.

Author: Acharya, Anushree, Kavus, Haluk, Dunn, Patrick, Nasir, Abdul, Folk, Leandra, Withrow, Kara, Wentzensen, Ingrid M., Ruzhnikov, Maura R. Z., Fallot, Camille, Smol, Thomas, Rama, Mélanie, Brown, Kathleen, Whalen, Sandra, Ziegler, Alban, Barth, Magali, Chassevent, Anna, Smith-Hicks, Constance, Afenjar, Alexandra, Courtin, Thomas, and Heide, Solveig
Abstract: Background Variants in HECW2 have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined. Methods Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a HECW2-related neurodevelopmental disorder. Results We identified 13 novel missense variants in HECW2 in 22 unpublished cases, of which 18 were confirmed to have a de novo variant. In addition, we reviewed the genotypes and phenotypes of previously reported and new cases with HECW2 variants (n=35 cases). All variants identified are missense, and the majority of likely pathogenic and pathogenic variants are located in or near the C-terminal HECT domain (88.2%). We identified several clustered variants and four recurrent variants (p.(Arg1191Gln);p. (Asn1199Lys);p.(Phe1327Ser);p.(Arg1330Trp)). Two variants, (p.(Arg1191Gln);p.(Arg1330Trp)), accounted for 22.9% and 20% of cases, respectively. Clinical characterisation suggests complete penetrance for hypotonia with or without spasticity (100%), developmental delay/intellectual disability (100%) and developmental language disorder (100%). Other common features are behavioural problems (88.9%), vision problems (83.9%), motor coordination/movement (75%) and gastrointestinal issues (70%). Seizures were present in 61.3% of individuals. Genotype-phenotype analysis shows that HECT domain variants are more frequently associated with cortical visual impairment and gastrointestinal issues. Seizures were only observed in individuals with variants in or near the HECT domain. Conclusion We provide a comprehensive review and expansion of the genotypic and phenotypic spectrum of HECW2 disorders, aiding future molecular and clinical diagnosis and management. [ABSTRACT FROM AUTHOR]
Published: 2022
Full Text: View/download PDF

44. Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders

Author: Zhang, David, primary, Guelfi, Sebastian, additional, Garcia-Ruiz, Sonia, additional, Costa, Beatrice, additional, Reynolds, Regina H., additional, D’Sa, Karishma, additional, Liu, Wenfei, additional, Courtin, Thomas, additional, Peterson, Amy, additional, Jaffe, Andrew E., additional, Hardy, John, additional, Botía, Juan A., additional, Collado-Torres, Leonardo, additional, and Ryten, Mina, additional
Published: 2020
Full Text: View/download PDF

45. Characterization of recessive Parkinson's disease in a large multicenter study

Author: Lesage, Suzanne, Lunati, Ariane, Houot, Marion, Romdhan, Sawssan, Clot, Fabienne, Tesson, Christelle, Mangone, Graziella, Le Toullec, Benjamin, Courtin, Thomas, Larcher, Kathy, Benmahdjoub, Mustapha, Arezki, Mohammed, Bouhouche, Ahmed, Anheim, Mathieu, Roze, Emmanuel, Viallet, François, Tison, François, Broussolle, Emmanuel, Emre, Murat, Hanagasi, Hasmet, Bilgic, Basar, Tazir, Meriem, Djebara, Mouna, Gouider, Riadh, Tranchant, Christine, Vidailhet, Marie, Le Guern, Eric, Corti, Olga, Mhiri, Chokri, Lohmann, Ebba, Singleton, Andrew, Corvol, Jean-Christophe, Brice, Alexis, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Mohammed V de Rabat [Agdal] (UM5), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Istanbul University, and National Institutes of Health [Bethesda] (NIH)
Subjects: [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], genotype-phenotype correlations, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, PINK1, [SCCO.NEUR]Cognitive science/Neuroscience, Parkinson’s disease, PRKN, autosomal recessive inheritance
Abstract: International audience; Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene‐targeting approaches for Parkinson disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ‐1 mutations in a cohort of 1,587 cases. Mutations were found in 14.1% of patients; 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians, whereas PINK1 mutations predominated in Arab‐Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa‐induced motor complications, dysautonomia, and dementia than those without mutations
Published: 2020
Full Text: View/download PDF

46. Heterozygous variants in MYH10associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling

Author: Holtz, Alexander M., VanCoillie, Rachel, Vansickle, Elizabeth A., Carere, Deanna Alexis, Withrow, Kara, Torti, Erin, Juusola, Jane, Millan, Francisca, Person, Richard, Guillen Sacoto, Maria J., Si, Yue, Wentzensen, Ingrid M., Pugh, Jada, Vasileiou, Georgia, Rieger, Melissa, Reis, André, Argilli, Emanuela, Sherr, Elliott H., Aldinger, Kimberly A., Dobyns, William B., Brunet, Theresa, Hoefele, Julia, Wagner, Matias, Haber, Benjamin, Kotzaeridou, Urania, Keren, Boris, Heron, Delphine, Mignot, Cyril, Heide, Solveig, Courtin, Thomas, Buratti, Julien, Murugasen, Serini, Donald, Kirsten A., O’Heir, Emily, Moody, Shade, Kim, Katherine H., Burton, Barbara K., Yoon, Grace, Campo, Miguel del, Masser-Frye, Diane, Kozenko, Mariya, Parkinson, Christina, Sell, Susan L., Gordon, Patricia L., Prokop, Jeremy W., Karaa, Amel, Bupp, Caleb, and Raby, Benjamin A.
Abstract: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.
Published: 2022
Full Text: View/download PDF

47. Genetic diagnosis of intellectual disability: results of trio-based whole exome sequencing in a cohort of 818 patients

Author: Courtin, Thomas, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Delphine Héron
Subjects: Exome sequencing, Déficience intellectuelle, Séquençage d’exome, MESH: Sequence Analysis, intellectual disability, Genetics, Diagnostic étiologique, Génétique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: intellectual disability (ID) is a clinically and genetically heterogeneous condition that affects 1 to 3% of the population worldwide. Recent improvements of next generation sequencing are giving rise to a drastic change in our medical approach. We present here the clinical and genetical characteristics of a large cohort of patients suffering from ID and which had a trio-based whole exome sequencing (WES). Patients and methods: 818 patients were recruited through clinical genetic and/or neuro-pediatric consultations. ID was assessed based on neuropsychological tests when available, DSM-5 classification was used otherwise. Prior to WES, DNA micro-array, Fragile-X syndrome testing and targeted-gene analysis in case of high syndromic suspicion were performed. If negative, trio-based WES was proposed. Molecular results were discussed in multidisciplinary team meetings before feed-back to patients. Results: the global diagnostic yield was 41% across all patients (338/818 patients). 41 variants were found in candidate genes and contributed to their validation as “ID genes”, rising the potential diagnostic yield to 47% (379/818 patients). Dominant variants were pre-eminent (81%) and most of them were de novo (95%) affecting 224 unique genes. Interestingly, the severity of ID had no significative effect on the diagnostic rate (mild ID, 66/180, 37% - moderate to profound ID, 108/419, 44%, p-value = 0.1997). Epilepsy and family history of ID were not identified neither as cofounding factors (p-value = 0.132 and 0.516). Conclusion: this study emphasizes the considerable genetic heterogeneity of ID and confirms the efficiency of trio-based WES for its exploration.; Introduction : la déficience intellectuelle (DI) est une affection cliniquement et génétiquement hétérogène qui concerne 1 à 3 % de la population mondiale. Des études récentes estiment qu’une origine génétique pourrait être retrouvée dans près de 60% de ces patients. Nous présentons ici les caractéristiques cliniques et génétiques d’une cohorte de patients atteints de DI et ayant bénéficié d’un séquençage d’exome en trio. Patients et méthodes : 818 patients ont été inclus à partir de 2016 par le biais de consultations de génétique médicale et/ou neuro-pédiatrique. La DI était évaluée sur la base d’un bilan neuropsychologique ou une échelle adaptative lorsque disponible. L’ensemble des patients ont bénéficié, avant séquençage d’exome, d’une Analyse Chromosomique sur Puce à ADN (ACPA) ainsi que d’une recherche d’X-fragile. Résultats : le taux diagnostique global de l’étude a été de 41 % (338/818 patients). 41 variants ont été identifiés dans des gènes candidats de DI et ont contribué à leur validation en tant que gène de DI augmentant le taux diagnostique à 47% (379/818 patients). De façon surprenante, la sévérité de la DI n’a pas eu d’impact significatif sur le taux diagnostique (léger ID, 66/180, 37% - modéré à sévère ID, 108/419, 44%, p-value = 0.1997). D’autres paramètres, comme l’histoire familiale, l’épilepsie non pas été identifiés non plus comme potentiels facteurs influençant l’efficacité diagnostique du WES (p-value = 0.132 and 0.516). Conclusion : cette étude souligne l’hétérogénéité génétique majeure de la DI et confirme l’intérêt d’une approche par séquençage d’exome en trio dans le cadre de prise en charge étiologique.
Published: 2019

48. Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders

Author: Zhang, David, Guelfi, Sebastian, Garcia-Ruiz, Sonia, Costa, Beatrice, Reynolds, Regina H., D'Sa, Karishma, Liu, Wenfei, Courtin, Thomas, Peterson, Amy, Jaffe, Andrew E., Hardy, John, Botia, Juan A., Collado-Torres, Leonardo, Ryten, Mina, Zhang, David, Guelfi, Sebastian, Garcia-Ruiz, Sonia, Costa, Beatrice, Reynolds, Regina H., D'Sa, Karishma, Liu, Wenfei, Courtin, Thomas, Peterson, Amy, Jaffe, Andrew E., Hardy, John, Botia, Juan A., Collado-Torres, Leonardo, and Ryten, Mina
Abstract: Growing evidence suggests that human gene annotation remains incomplete; however, it is unclear how this affects different tissues and our understanding of different disorders. Here, we detect previously unannotated transcription from Genotype-Tissue Expression RNA sequencing data across 41 human tissues. We connect this unannotated transcription to known genes, confirming that human gene annotation remains incomplete, even among well-studied genes including 63% of the Online Mendelian Inheritance in Man-morbid catalog and 317 neurodegeneration-associated genes. We find the greatest abundance of unannotated transcription in brain and genes highly expressed in brain are more likely to be reannotated. We explore examples of reannotated disease genes, such as SNCA, for which we experimentally validate a previously unidentified, brain-specific, potentially protein-coding exon. We release all tissue-specific transcriptomes through vizER: http://rytenlab.com/browser/app/vizER . We anticipate that this resource will facilitate more accurate genetic analysis, with the greatest impact on our understanding of Mendelian and complex neurogenetic disorders.
Published: 2020

49. Further delineation of the phenotypic spectrum associated with hemizygous loss‐of‐function variants in NONO

Author: Sewani, Maham, primary, Nugent, Kimberly, additional, Blackburn, Patrick R., additional, Tarnowski, Jessica M., additional, Hernandez‐Garcia, Andres, additional, Amiel, Jeanne, additional, Whalen, Sandra, additional, Keren, Boris, additional, Courtin, Thomas, additional, Rosenfeld, Jill A., additional, Yang, Yaping, additional, Patterson, Marc C., additional, Pichurin, Pavel, additional, McLean, Scott D., additional, and Scott, Daryl A., additional
Published: 2019
Full Text: View/download PDF

50. Genetic and Phenotypic Characterisation of Autosomal Recessive Parkinson's Disease in a Large Multicentre Cohort

Author: Lesage, Suzanne, primary, Lunati, Ariane, additional, Houot, Marion, additional, Benromdhan, Sawssan, additional, Clot, Fabienne, additional, Tesson, Christelle, additional, Mangone, Graziella, additional, Le Toullec, Benjamin, additional, Courtin, Thomas, additional, Larcher, Kathy, additional, Benmahdjoub, Mustapha, additional, Arezki, Mohammed, additional, Bouhouche, Ahmed, additional, Anheim, Mathieu, additional, Roze, Emmanuel, additional, Viallet, François, additional, Tison, François, additional, Broussolle, Emmanuel, additional, Emre, Murat, additional, Tazir, Meriem, additional, Tranchant, Christine, additional, Vidailhet, Marie, additional, Le Guern, Eric, additional, Corti, Olga, additional, Mhiri, Chokri, additional, Lohmann, Ebba, additional, Singleton, Andrew B., additional, Corvol, Jean-Christophe, additional, Brice, Alexis, additional, and Group (PDG), French Parkinson’s Disease Genetics, additional
Published: 2019
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

136 results on '"Courtin, Thomas"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources