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33 results on '"D'Amours, G"'

5. Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability

Author

Verheije, R., Kupchik, G.S., Isidor, B., Kroes, H.Y., Lynch, S.A., Hawkes, L., Hempel, M., Gelb, B.D., Ghoumid, J., D’Amours, G., Chandler, K., Dubourg, C., Loddo, S., Tümer, Z., Shaw-Smith, C., Nizon, M., Shevell, M., Van Hoof, E., Anyane-Yeboa, K., Cerbone, G., Clayton-Smith, J., Cogné, B., Corre, P., Corveleyn, A., De Borre, M., Hjortshøj, T.D., Fradin, M., Gewillig, M., Goldmuntz, E., Hens, G., Lemyre, E., Journel, H., Kini, U., Kortüm, F., Le Caignec, C., Novelli, A., Odent, S., Petit, F., Revah-Politi, A., Stong, N., Strom, T.M., van Binsbergen, E., DDD Study, Devriendt, K., and Breckpot, J.

Subjects
Male, Loss of Function Mutation, Intellectual disability, Genetics(clinical), Non-U.S. Gov't, Child, Genetics (clinical), Heart Defects, Genetics, 0303 health sciences, Congenital/genetics, Research Support, Non-U.S. Gov't, 030305 genetics & heredity, Syndrome, Phenotype, Heart Defects, Congenital/genetics, Cleft Palate, Child, Preschool, Female, Haploinsufficiency, Heart Defects, Congenital, Heterozygote, Adolescent, Transcription Factors/genetics, Locus (genetics), Research Support, Article, N.I.H, 03 medical and health sciences, Young Adult, Research Support, N.I.H., Extramural, Cleft Palate/genetics, Intellectual Disability, medicine, Journal Article, Humans, Preschool, Gene, Loss function, Homeodomain Proteins, business.industry, Chromosome, Extramural, Heterozygote advantage, medicine.disease, Intellectual Disability/genetics, Homeodomain Proteins/genetics, business, Transcription Factors
Abstract

Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype–phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.

Published
2018

8. Refining the phenotype associated with biallelic DNAJC21 mutations

Author

D'Amours, G., primary, Lopes, F., additional, Gauthier, J., additional, Saillour, V., additional, Nassif, C., additional, Wynn, R., additional, Alos, N., additional, Leblanc, T., additional, Capri, Y., additional, Nizard, S., additional, Lemyre, E., additional, Michaud, J.L., additional, Pelletier, V.-A., additional, Pastore, Y.D., additional, and Soucy, J.-F., additional

Published
2018
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11. Fog fever

Author

D'Amours, Genevieve

Published
2023

12. Application of LS-DYNA SPH Formulation to Model Semi-Solid Metal Casting

Author

Pineau, F. and D’Amours, G.

Subjects
Application of LS-DYNA SPH Formulation, Modelling, Semi-Solid Metal Casting, alloys
Abstract

Semisolid metal alloys have a special microstructure of globular grains suspended in a liquid metal matrix. This particular physical state of the matter can be exploited to produce near-net-shape parts with improved mechanical properties. Indeed, semi-solid processes take advantage of a much higher apparent viscosity of the die cast materials by limiting the risk of oxide formed on the free surfaces to become incorporated into the casting when the material is injected into the die. Semi-solid processes that use billets as feedstock material are however tied up with an additional type of surface contamination. During the injection phase, the external-skin on the periphery of the billet, which has been in contact with air and lubricant during the transfer in the shot sleeve may be incorporated into the casting. This can be an important cause of reject for most structural parts in the automotive industry. In order to predict and control the occurrence of skin inclusion into cast parts during the injection phase of semisolid processes, Lagrangian methods are appropriate. Indeed, the skin, composed of contaminated or even partially solidified metal, has different mechanical properties compared to the core of semi-solid aluminum. Abitrary- Lagrangian-Eulerian formulations, which can account for the coupling between the “solid” skin and the flow of “semi-solid” aluminum are promising but still necessitate a huge amount of computer power. On the other hand, particle based Smoothed Particle Hydrodynamics (SPH) approaches are particularly well suited to this kind of flows involving complex flow behavior and solidification. These methods are able to track accurately free surface flows with fragmentation and break up as well as to follow the advection of oxides through the flow. In this paper, a first analysis is performed in order to investigate the potential of the SPH solver of LS-DYNA to deal with the problem of skin inclusion in semi-solid die casting processes. Preliminary results show that the SPH approach is a very promising simulation tool to follow the skins during semi-solid injection casting., 8th European LS-DYNA Conference, Strasbourg, France, May 22-23, 2011, Strasbourg, France

Published
2011

13. Heat transfer Simulation to determine the impact of Al-5Mg arc sprayed coating onto 7075 T6 alloy fatigue performance

Author

D'Amours, G., Arsenault, B., Breton, F., and Dubé, D.

Subjects
7075 T6 Alloy, Heat transfer simulation, alliage, aluminum, transfert de chaleur, déposition à l'arc, aluminium, Fatigue performance, Al5-Mg, revêtement, Arc spray coating
Abstract

Aluminum-5% magnesium coatings was deposited by arc spraying onto aircraft Al 7075 T651 structural alloy for corrosion protection while required to maintain the substrate material fatigue performance integrity. Fatigue performance of coating system is complex and in order to better understand the variability of the fatigue performance of coatings, heat flow in substrate was studied and simulated to determine the temperature evolution during arc spraying in both substrate and coating for different process parameters. Experimental temperature measurements, theoretical calculations and simulation were carried out to extrapolate the coating temperature with respect to coating process variables and surface preparation. Both flux and conductance were identified by an inverse method to reproduce experimental temperature measurements. The thermal transient solver of LS-DYNA® was used to simulate the time-dependence of heat flux in the coating during successive depositions. The benefit of that model is its capability to predict the temperature distribution and evolution in time in a sample. Samples were made of Al 7075 T651 alloy and were 80 mm in length by 25 mm wide and 7 mm thick. A coating thickness of 250 μm was reached. It was the spray thermal energy that was taken into account in the model as the thermal load. The quality of the thermal contact between the substrate and coating was also included in the model and conductance was defined to control the amount of heat transferred at the interface. Coating performance was evaluated in term of fatigue properties, bond strength, and interface quality of as deposited coatings. The superior fatigue resistance of the coated alloy relies on low heat input process parameters and surface preparation that favor high interface conductance to keep low coating temperature during the coating process. Surface preparation, arc current and atomizing gases play all a key role to provide a fatigue resistant coating., 11th International LS-DYNA Users Conference, LSTC, June 6-8, 2010, Dearborn, Michigan, USA

Published
2010

15. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction

Author

Van de Werf, F., Armstrong, P. W., Granger, C., Wallentin, L., Adgey, A. A. J., Aylward, P., Binbrek, A. S., Califf, R., Cassim, S., Diaz, R., Fanebust, R., Fioretti, P. M., Huber, K., Husted, S., Lindahl, B., Lopez-Sendon, J. L., Makijarvi, M., Meyer, J., Navarro Robles, J., Pfisterer, M., Seabra-Gomes, R., Soares-Piegas, L., Sugrue, D., Tendera, M., Theroux, P., Toutouzas, P., Vahanian, A., Verheugt, F., Sarelin, H., Goetz, G., Bluhmki, E., Daclin, V., Danays, T., Houbracken, K., Kaye, J., Reilly, P., Hacke, W., von Kummer, R., Lesaffre, E., Bogaerts, K., Peeters, C., Fox, K. A. A., Brower, R., Hirsh, J., Maggioni, A., Tijssen, J., Weaver, D., Beernaert, A., Beysen, N., Broos, K., De Prins, E., D'Hollander, K., Dupon, L., Fomyna, N., Fransen, A., Genesse, D., Goffin, L., Hendrickx, R., Jansen, B., Jorissen, F., Luys, C., Luyten, A., Marschal, C., Moreira, M., Munsters, K., Salerno, R., Schoovaerts, C., Sinnaeve, P., Schildermans, C., Vandenberghe, K., Vandeschoot, K., Van Gucht, H., Van Rompaey, P., Vlassak, S., Watzeels, M., Wittockx, H., Galan, K., Humeniuk, L., Seidel, A., Molina, M., Hafley, G., Alexander, J., Pascual, A., Bestilny, S., Temple, T., Ahuad Guerrero, R., Albisu, J. P., Bassani Arrieta, C. A., Bono, J., Caccavo, A., Cagnolatti, A., Cartasegna, L. R., Castellanos, R., Chekerdemian, S., Covelli, G., Cuello, J. L., Cuneo, C. A., Fernandez, A., Ferrara, C., Ferro-Queirel, E., Gambarte, A., Garcia-Duran, R., Hasbani, E., Hrabar, A., Keller, L., Lobo Marquez, L. L., Luciardi, H., Macin, S. M., Marinig, A., Marzetti, E., Muntaner, J., Nordaby, R., Orlandini, A. D., Piombo, A. C., Pomposiello, J. C., Quijano, R. A., Amerena, J., Aroney, G., Buckmaster, N., Carroll, P., Fitzpatrick, M., Newman, R., Rowe, M., Singh, B., Thomson, A., Winter, C., Eber, B., Gaul, G. B., Klein, W., Leisch, F., Mayr, H., Mlczoch, J., Niessner, H., Pachinger, O., Pall, H., Pichler, M., Roggla, G., Schaflinger, E., Schreiber, W., Slany, J., Traindl, O., Zenker, G., Beckers, J., Bekaert, I., Berthe, C., Bodur, G., Carlier, B., Carlier, M., Carpentier, J., Celen, H., Charlier, F., Clement, A., Coenen, A., Crochelet, L., De Keyser, F., De Man, F., de Meester, A., Dendale, P., Dhondt, E., Dhooghe, G., El Allaf, D., Elshot, S., Emmerechts, C., Foret, F., Gatera, E., Geraedts, J., Gerardy, A. C., Gysbrechts, M., Hallemans, R., Hellemans, S., Herssens, H., Huygens, L., Janssens, L., Lalmand, J., Maamar, R., Marechal, P., Mertens, D., Michel, P., Morandini, E., Nannan, M., Nguyen, D., Odeurs, W., Peerenboom, P., Pirenne, B., Quinonez, M., Raymenants, E., Renard, M., Silance, P. G., Standaert, A. M., Striekwold, H., Thiels, H., Valadi, D., van Brabandt, H., Van Dormael, M., Van Iseghem, P., Van Walleghem, U., Vanden Bosch, H., Vandenbossche, J. L., Vermylen, J., Verstraete, S., Vo Ngoc, P., Willems, P., Zenner, R., Campos de Albuquerque, D., Coutinho, M., de Camargo Carvalho, A. C., Fernandes Manenti, E. R., Ferreira Azevedo, A., Golin, V., Gun, C., Marin Neto, J. A., Marino, R. L., Miranda Abrantes, J. A., Nicolau, J. C., Porto Alegre Dancini, E. M., Rabelo, A., Ramos, R. F., Rizzi Coelho, O., Alexander, D., Bata, I. R., Bhargava, R. K., Bogaty, P., D'Amours, G., Darcel, I., Finnie, K. J. C., Fowlis, R., Gupta, M. K., Henderson, M., Howlett, M. K., Javier, J. J., Kieu, C. V., Kumar, G., Lebouthillier, P., Leduc, F., Lepage, S., Mcavinue, T., Mcgillen, J. E., Mcmeekin, J. D., Morse, J. W., Pistawka, K., Raimondo, E. F., Sandrin, F., Smith, H., Smylie, P. C., Tran, K., Turabian, M., Wagner, K. R., Winkler, L. H., Woo, K. S., Falstie-Jensen, N., Lind Rasmussen, S., Lomholt, P., Markenvard, J., Nielsen, H., Petersen, J., Romer, F., Ahonen, J., Huttunen, M., Kokkonen, L., Luukkonen, J., Mantyla, P., Melin, J., Mustonen, J., Valli, J., Voutilainen, S., Agraou, B., Allam, S., Baradat, G., Battistella, P., Bazin, P., Bouvier, J. -M., Destrac, S., Fouche, R., Fournier, P. -Y., Funck, F., Garnier, H., Grall, J. -Y., Gully, C., Lallement, P. -Y., Loiselet, P., Mycinsky, C., Page, A., Parisot, M., Range, G., Rocher, R., Tafani, C., Thisse, J. -Y., Tibi, T., Tissot, M., Wahl, P., Backenkohler, U., Bavastro, P., Beckmann-Hiss, H., Behnke, M., Bermes, M., Bernsmeier, R., Bethge, K. P., Bethge, H., Block, M., Burkhardt, W., Cieslinski, G., Claus, G., Deetjen, A., Diefenbach, A., Diehm, C., Dietz, A., Dippold, W. G., Eichner, A., Erckenbrecht, J. F., Gawlick, L., Gerber, V., Goppel, L., Gottwik, M., Grosch, B., Hammer, B., Hanheide, M., Hanrath, P., Haspel, J., Hennersdorf, F., Hermanns, M., Hoffmeister, H. M., Holzapfel, P., Hubner, H., Jansen, W., Jung, S., Kaddatz, J., Kienbock, H., Klein, H. H., Konz, K. H., Kulschbach, M., Leschke, M., Liebau, G., Linnartz, M., Lockert, G., Loesbrock, R., Lollgen, H., Ludwig, N., Mudra, H., Munzer, K., Nebel, B., Nellessen, U., Neu, C., Olbrich, H. G., Pfeffer, A., Pfeiffer, P., Plate, V., Pollock, B., Rapp, H., Rommele, U., Sauer, K., Scheffler, N., Schlotterbeck, K., Schmidt-Salzmann, A., Schnitzler, G., Schumann, H., Schuster, C. J., Schuster, P., Schweizer, P., Seitz, K., Simon, R., Spes, C., Szabo, S., Terhardt-Kasten, E., Theuerkauf, B., Tigges, R., Tinnappel, J., Topp, H., Trockel, P., Unland, N., Veth, V., Vom Dahl, J., Vossbeck, G., Weindel, K., Weib, D., Wiewel, D., Wirtz, P., Zipp, C., Apostolou, T., Chalkidis, C., Exadaktylos, N., Foussas, S., Hatseras, D., Karas, S., Karydis, K., Lambrou, S., Louridas, G., Manolis, A., Nanas, J., Novas, I., Panagiotidou, T., Papadopoulos, C., Papakonstantinou, D., Papasteriadis, E., Pavlidis, P., Pyrgakis, V., Skoufas, P., Stavrati, A., Tyrologos, A., Vardas, P., Vrouchos, G., Zacharoulis, A., Zarifis, J., Brown, A., Daly, K., Fennell, W., Horgan, J., Mccann, H., Mcdonald, K., O'Reilly, M., Sullivan, P., Altamura, G., Ambrosio, G., Auteri, A., Aveta, P., Azzarito, M., Badano, L. P., Barbiero, M., Barletta, C., Biscosi, C., Boccanelli, A., Bottero, M., Brizio, E., Brunazzi, M. C., Brunelli, C., Bugatti, U., Capozi, A., Capucci, A., Carfora, A., Caronna, A., Carrone, M., Casazza, F., Cauticci, A., Ceci, V., Ciconte, V., Circo, A., Ciricugno, S., Comito, F., Cornacchia, D., Corsini, G., D'Andrea, F., De Rosa, P., De Simone, M., Del Citerna, F., Del Pinto, M., Dell'Ali, C., Della Casa, S., Della Monica, R., Delogu, G., Di Biase, M., Di Chiara, A., Di Guardo, G., Di Marco, S., Di Mario, F., Di Napoli, T., Di Palma, F., Fadin, B. M., Fazzari, M., Ferraiuolo, G., Fiaschetti, R., Fontanelli, A., Fresco, C., Gambelli, G., Gasbarri, F., Gemelli, M., Giani, P., Gigantino, A., Giomi, A., Giorgi, G., Greco, C., Gregorio, G., Guagnozzi, G., Guiducci, U., Guzzardi, G., Izzo, A., La Rosa, A., Leone, F., Leone, G., Lo Bianco, F., Locuratolo, N., Maggiolini, S., Malinconico, M., Mancone, C., Mangiameli, S., Marchi, S. M., Maresta, A., Mauri, F., Mazzini, C. A., Michisanti, M., Miracapillo, G., Modena, M. G., Morgagni, G. L., Mossuti, E., Nascimbeni, F., Negrelli, M., Notaristefano, A., Pardi, S., Peci, P., Pettinati, G., Pietropaolo, F., Pirelli, S., Pretolani, M., Prinzi, D., Proietti, F., Raganelli, L., Rapino, S., Re, F., Ricci, R., Rinaldi, G., Rusticali, G., Severi, S., Spallarossa, P., Tartagni, F., Terrosu, P., Tortorella, G., Tota, F., Tritto, I., Tuccilo, B., Turco, V., Uscio, G., Valagussa, F., Vergoni, W., Verzuri, M. S., Vetrano, A., Villani, R., Zanini, R., Boisante, L., Niclou, R., Alcocer, L., Castro, A., Fragoso, J., Gonzalez, V., Gonzalez-Pacheco, H., Hernandez-Santamaria, I., Huerta, R., Huerta, D., Martinez, A., Mendoza, M., Moguel, R., Navarro, J., Portos, J. M., Rodriguez, I., Sierra, L., Valencia, S., Vazquez, A., Arnold, A. E. R., Boehmer, A. G., de Graaf, J. J., Funke Kupper, A. J., Gobel, E. J. A. M., Janus, C. L., Linssen, G. C. M., Sedney, M. I., Slegers, L. C., Spierenburg, H. A. M., Strikwerda, S., Tans, J. G. M., Twisk, S. P. M., van der Heijden, R., van Kalmthout, P. M., Verheugt, F. W. A., Holt, E., Skogsholm, A., Thorshaug, R., Thybo, N. K., Wang, H., Maciejewicz, J., Piotrowski, W., Pluta, W., Ruminski, W., Skura, M., Smielak-Korombel, W., Carranca, J., Carvalho, M., Catarino, C., Cunha, D., Ferreira, D., Ferreira, J., Ferreira da Costa, A. F., Lopes de Carvalho, J., Martins, L., Mourao, L., Oliveira Carrageta, M., Prazeres de Sa, E., Puig, J., Ramalho Dos Santos, M. J. J., Resende, M., Seabra Gomes, R., Baig, M. M. E., Bayat, J., Benjamin, J. D., Ranjith, N., Routier, R., Wittmer, H., Abizanda Campos, R., Alonso Garcia, M. A., Amaro Cendon, A., Arboleda Sanchez, J. A., Blanco Varela, J., Bruguera I Cortada, J., Carpintero Avellaneda, J. L., Caturla Such, J., Civeira Murillo, E., Fernandez Aviles, F., Fernandez Fernandez, R., Figueras Bellot, J., Fiol Sala, M., Froufe Sanchez, J., Garcia Calabozo, R., Garcia Palacios, J. L., Gonzalez Maqueda, I., Kallmeyer Martin, C., Lopez Sendon, J. L., Manzano Ramirez, A., Marine Rebull, J., Monton Rodriguez, A., Pique Gilart, M., Reina Toral, A., Rodriguez Llorian, A., Ruano Marco, M., Sanchez Miralles, A., Sanjose Garagarza, J. M., Santalo Bel, M., Torres Ruiz, J. M., Valentin Segura, V., Ahlstrom, P., Ahremark, U., Bandh, S., Bellinetto, A., Dahlberg, A., Hansen, O., Hurtig, U., Jonasson, L., Karlsson, J. E., Larsson, L. E., Moller, B., Ohlin, H., Persson, H., Sandstedt, L., Soderberg, S., Svennberg, L., Swahn, E., Tygesen, H., Broccard, A. F., Estlinbaum, W., Follath, F., Frutiger, A., Hess, N., Maggiorini, M., Marti, D., Muller, P., Rickenbacher, P., Schaller, M. D., Weinbacher, M., Abdulali, S., Ahmad, G., George, S., Ghazi, A., Rao, K. N., Bishop, A., Bridges, A., Canepa-Anson, R., Cave, M., Clarck, R., Cooper, I., de Belder, A., Farrer, M., Kendall, J. M., Ludman, P., Mattu, R., Mcglinchey, P., Moriarty, A. J., Muthusamy, S., Nee, P. A., Nolan, J., Papouchado, M., Rose, E. L., Shahi, M., Stephens, J., Trevelyan, J., Abdul-Karim, A., Adler, L., Arunasalam, S., Avington, D., Baron, S., Beel, T., Bellamy, B., Bennett, J., Berndt, T., Berrick, A., Bersin, R. M., Bethala, V., Bharath, S., Bouchard, A., Boulet, J. E., Bowerman, R., Boyek, T., Brar, R. S., Brodell, G., Bryant, B., Buckner, J. K., Cage, J., Cannon, J. D., Carducci, B., Carr, K., Chang, M., Chelliah, N., Chin, W. L., Chin, J., Church, D. H., Clark, R., Coulis, L., Dadkhah, S., Dearing, B., Defranco, A., Dharawat, M., Dharawat, R., Dhruva, N., Dicola, J., Dykstra, G., Eisenberg, S., El-Bialy, A., Fera, S., Ford, K., Foreman, R. D., Friedman, S., Friedman, V., Garibian, G., Gelormini, J., Geninatti, M. R., Genovese, R., Ghazi, F., Gilchrist, I., Gitler, B., Glover, R., Gonzalez, J., Goulah, R., Graham, B., Gray, R., Grodman, R., Habib, G. B., Hack, T., Hamroff, G., Hanna, G., Hart, M., Haught, H., Hawkins, J., Hempel, R., Hiremath, Y., Hiser, W., Holland, E., Jaffe, N., Jamal, N., James, K. F., Kalla, S., Kates, M., Kemper, A. J., Kennedy, J. J., Kerut, E. K., Killpack, M., King, J., T. Y., Ko, Kollar, K., Kontos, M., Kugelmassluu, A., Kumar, A., Kutscher, A. H., Lambrecht, C., Lancaster, L., Layden, J., Lazar, A., Lebow, M., Lee, C., Lee, A. B., Lehr, J., Levin, F. L., Levitt, R., Levy, R. M., Lieberman, A., Litman, G. I., Lui, H., Luu, M. Q., Macdonald, G., Madyoon, H., Mancherje, C., Marmulstein, M., Mclaurin, B. T., Mcnellis, M., Mendelson, R., Micale, P. J., Miller, M. J., Miller, M. S., Miller, J., Millman, A., Millsaps, R., Minor, S., Modica, J., Morse, H., Moskovits, N., Nester, B. A., Newton, A. S., Niazi, I., Niederman, A., Oatfield, R., Painter, J. A., Pamfilis, S. M., Pamulapati, K. M., Patel, N., Payne, R., Pearson, C., Peizner, D. S., Petrovich, L., Piriz, J., Pollack, M., Pollock, S., Popkave, A., Puma, J. A., Quesada, R., Quigley-Malcolm, D., Raby, K., Ravindran, K., Rees, A. P., Reiner, J., Rivera, E., Rogers, F., Rosenthal, A., Rowe, W. W., Ryan, P. F., Ryman, K., Salacata, A., Santolin, C., Saucedo, J., Savage, R., Savage, W., Schumacher, R., Segarra, S., Sharkey, S., Shonkoff, D., Silver, M., Silver, S. L., Singh, G., Sinyard, R. D., Sporn, D., Srivastava, N. K., Stomel, R., Suresh, D. P., Tallman, M., Togioka, T., Varma, S., Verant, R. P., Wallach, R., Weinberg, M., Weinberg, D., Weinstein, J. M., Wesley, G., Westerman, J. H., Wheeling, J., Whitaker, J., Widmer, M., Yasin, M., and Zakrzewski, M. J.

Subjects
Male, medicine.medical_specialty, Abciximab, Ischemia, Myocardial Infarction, Tenecteplase, Injections, Immunoglobulin Fab Fragments, Reperfusion therapy, Fibrinolytic Agents, Recurrence, Internal medicine, medicine, Humans, Myocardial infarction, Enoxaparin, Aged, Intention-to-treat analysis, Chi-Square Distribution, business.industry, Heparin, Antibodies, Monoclonal, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Regimen, Treatment Outcome, Anesthesia, Tissue Plasminogen Activator, Cardiology, Drug Therapy, Combination, Female, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

BACKGROUND: Current fibrinolytic therapies fail to achieve optimum reperfusion in many patients. Low-molecular-weight heparins and platelet glycoprotein IIb/IIIa inhibitors have shown the potential to improve pharmacological reperfusion therapy. We did a randomised, open-label trial to compare the efficacy and safety of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase plus weight-adjusted unfractionated heparin in patients with acute myocardial infarction. METHODS: 6095 patients with acute myocardial infarction of less than 6 h were randomly assigned one of three regimens: full-dose tenecteplase and enoxaparin for a maximum of 7 days (enoxaparin group; n=2040), half-dose tenecteplase with weight-adjusted low-dose unfractionated heparin and a 12-h infusion of abciximab (abciximab group; n=2017), or full-dose tenecteplase with weight-adjusted unfractionated heparin for 48 h (unfractionated heparin group; n=2038). The primary endpoints were the composites of 30-day mortality, in-hospital reinfarction, or in-hospital refractory ischaemia (efficacy endpoint), and the above endpoint plus in-hospital intracranial haemorrhage or in-hospital major bleeding complications (efficacy plus safety endpoint). Analysis was by intention to treat. FINDINGS: There were significantly fewer efficacy endpoints in the enoxaparin and abciximab groups than in the unfractionated heparin group: 233/2037 (11.4%) versus 315/2038 (15.4%; relative risk 0.74 [95% CI 0.63-0.87], p=0.0002) for enoxaparin, and 223/2017 (11.1%) versus 315/2038 (15.4%; 0.72 [0.61-0.84], p

Published
2001

23. Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype.

Author

D'Amours, G, Kibar, Z, Mathonnet, G, Fetni, R, Tihy, F, Désilets, V, Nizard, S, Michaud, JL, and Lemyre, E

Subjects
*ETIOLOGY of diseases, *KARYOTYPES, *INTELLECTUAL disabilities, *COMPARATIVE genomic hybridization, *HUMAN abnormalities
Abstract

D'Amours G, Kibar Z, Mathonnet G, Fetni R, Tihy F, Désilets V, Nizard S, Michaud JL, Lemyre E. Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype. Despite a wide range of clinical tools, the etiology of mental retardation and multiple congenital malformations remains unknown for many patients. Array-based comparative genomic hybridization (aCGH) has proven to be a valuable tool in these cases, as its pangenomic coverage allows the identification of chromosomal aberrations that are undetectable by other genetic methods targeting specific genomic regions. Therefore, aCGH is increasingly used in clinical genetics, both in the postnatal and the prenatal settings. While the diagnostic yield in the postnatal population has been established at 10-12%, studies investigating fetuses have reported variable results. We used whole-genome aCGH to investigate fetuses presenting at least one major malformation detected on ultrasound, but for whom standard genetic analyses (including karyotype) failed to provide a diagnosis. We identified a clinically significant chromosomal aberration in 8.2% of tested fetuses (4/49), and a result of unclear clinical significance in 12.2% of tested fetuses (6/49). Our results document the value of whole-genome aCGH as a prenatal diagnostic tool and highlight the interpretation difficulties associated with copy number variations of unclear significance. [ABSTRACT FROM AUTHOR]

Published
2012
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24. Genetics Navigator: protocol for a mixed methods randomized controlled trial evaluating a digital platform to deliver genomic services in Canadian pediatric and adult populations.

Author

D'Amours G, Clausen M, Luca S, Reble E, Kodida R, Assamad D, Bernier F, Chad L, Costain G, Dhalla I, Faghfoury H, Friedman JM, Hewson S, Jamieson T, Silver J, Shuman C, Osmond M, Carroll JC, Jobling R, Laberge AM, Aronson M, Liston E, Lerner-Ellis J, Marshall C, Brudno M, Pham Q, Rudzicz F, Cohn R, Mamdani M, Smith M, Shastri-Estrada S, Seto E, Thorpe K, Ungar W, Hayeems RZ, and Bombard Y

Subjects
Humans, Adult, Child, Genetic Testing methods, Randomized Controlled Trials as Topic, Quality of Life, Ontario, Canada, Patient Navigation, Genetic Counseling methods
Abstract

Introduction: Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings., Methods and Analysis: We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives., Ethics and Dissemination: This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals., Trial Registration Number: NCT06455384., Competing Interests: Competing interests: YB and MC are cofounders of Genetics Adviser., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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27. Prenatal pleural effusions and chylothorax: An unusual presentation for CM-AVM syndrome due to RASA1.

Author

D'Amours G, Brunel-Guitton C, Delrue MA, Dubois J, Laberge S, and Soucy JF

Subjects
Adult, Allergens, Arteriovenous Malformations diagnosis, Arteriovenous Malformations pathology, Capillaries pathology, Chylothorax diagnosis, Chylothorax pathology, Female, Genetic Predisposition to Disease, Humans, Plant Proteins, Pleural Effusion diagnosis, Pleural Effusion pathology, Port-Wine Stain diagnosis, Port-Wine Stain pathology, Prenatal Diagnosis methods, Arteriovenous Malformations genetics, Capillaries abnormalities, Chylothorax genetics, Pleural Effusion genetics, Port-Wine Stain genetics, p120 GTPase Activating Protein genetics
Published
2020
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28. A variant of neonatal progeroid syndrome, or Wiedemann-Rautenstrauch syndrome, is associated with a nonsense variant in POLR3GL.

Author

Beauregard-Lacroix E, Salian S, Kim H, Ehresmann S, DʹAmours G, Gauthier J, Saillour V, Bernard G, Mitchell GA, Soucy JF, Michaud JL, and Campeau PM

Subjects
Child, Preschool, Female, Fetal Growth Retardation pathology, Humans, Phenotype, Progeria pathology, Protein Domains, RNA Polymerase III chemistry, Codon, Nonsense, Fetal Growth Retardation genetics, Progeria genetics, RNA Polymerase III genetics
Abstract

Neonatal progeroid syndrome, also known as Wiedemann-Rautenstrauch syndrome, is a rare condition characterized by severe growth retardation, apparent macrocephaly with prominent scalp veins, and lipodystrophy. It is caused by biallelic variants in POLR3A, a gene encoding for a subunit of RNA polymerase III. All variants reported in the literature lead to at least a partial loss-of-function (when considering both alleles together). Here, we describe an individual with several clinical features of neonatal progeroid syndrome in whom exome sequencing revealed a homozygous nonsense variant in POLR3GL (NM_032305.2:c.358C>T; p.(Arg120Ter)). POLR3GL also encodes a subunit of RNA polymerase III and has recently been associated with endosteal hyperostosis and oligodontia in three patients with a phenotype distinct from the patient described here. Given the important role of POLR3GL in the same complex as the protein implicated in neonatal progeroid syndrome, the nature of the variant identified, our RNA studies suggesting nonsense-mediated decay, and the clinical overlap, we propose POLR3GL as a gene causing a variant of neonatal progeroid syndrome and therefore expand the phenotype associated with POLR3GL variants.

Published
2020
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29. Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability.

Author

Verheije R, Kupchik GS, Isidor B, Kroes HY, Lynch SA, Hawkes L, Hempel M, Gelb BD, Ghoumid J, D'Amours G, Chandler K, Dubourg C, Loddo S, Tümer Z, Shaw-Smith C, Nizon M, Shevell M, Van Hoof E, Anyane-Yeboa K, Cerbone G, Clayton-Smith J, Cogné B, Corre P, Corveleyn A, De Borre M, Hjortshøj TD, Fradin M, Gewillig M, Goldmuntz E, Hens G, Lemyre E, Journel H, Kini U, Kortüm F, Le Caignec C, Novelli A, Odent S, Petit F, Revah-Politi A, Stong N, Strom TM, van Binsbergen E, Devriendt K, and Breckpot J

Subjects
Adolescent, Child, Child, Preschool, Cleft Palate pathology, Female, Heart Defects, Congenital pathology, Heterozygote, Homeodomain Proteins metabolism, Humans, Intellectual Disability pathology, Male, Phenotype, Syndrome, Transcription Factors metabolism, Young Adult, Cleft Palate genetics, Heart Defects, Congenital genetics, Homeodomain Proteins genetics, Intellectual Disability genetics, Loss of Function Mutation, Transcription Factors genetics
Abstract

Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.

Published
2019
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30. SNP arrays: comparing diagnostic yields for four platforms in children with developmental delay.

Author

D'Amours G, Langlois M, Mathonnet G, Fetni R, Nizard S, Srour M, Tihy F, Phillips MS, Michaud JL, and Lemyre E

Subjects
Adolescent, Child, Child, Preschool, Comparative Genomic Hybridization methods, Female, Gene Expression Profiling, Humans, Infant, Karyotyping, Male, Oligonucleotide Array Sequence Analysis methods, Phenotype, Biomarkers metabolism, DNA Copy Number Variations, Developmental Disabilities diagnosis, Developmental Disabilities genetics, Genome, Human, Loss of Heterozygosity, Polymorphism, Single Nucleotide genetics
Abstract

Background: Molecular karyotyping is now the first-tier genetic test for patients affected with unexplained intellectual disability (ID) and/or multiple congenital anomalies (MCA), since it identifies a pathogenic copy number variation (CNV) in 10-14% of them. High-resolution microarrays combining molecular karyotyping and single nucleotide polymorphism (SNP) genotyping were recently introduced to the market. In addition to identifying CNVs, these platforms detect loss of heterozygosity (LOH), which can indicate the presence of a homozygous mutation or uniparental disomy. Since these abnormalities can be associated with ID and/or MCA, their detection is of particular interest for patients whose phenotype remains unexplained. However, the diagnostic yield obtained with these platforms is not confirmed, and the real clinical value of LOH detection has not been established., Methods: We selected 21 children affected with ID, with or without congenital malformations, for whom standard genetic analyses failed to provide a diagnosis. We performed high-resolution SNP array analysis with four platforms (Affymetrix Genome-Wide Human SNP Array 6.0, Affymetrix Cytogenetics Whole-Genome 2.7 M array, Illumina HumanOmni1-Quad BeadChip, and Illumina HumanCytoSNP-12 DNA Analysis BeadChip) on whole-blood samples obtained from children and their parents to detect pathogenic CNVs and LOHs, and compared the results with those obtained on a moderate resolution array-based comparative genomic hybridization platform (NimbleGen CGX-12 Cytogenetics Array), already used in the clinical setting., Results: We identified a total of four pathogenic CNVs in three patients, and all arrays successfully detected them. With the SNP arrays, we also identified a LOH containing a gene associated with a recessive disorder consistent with the patient's phenotype (i.e., an informative LOH) in four children (including two siblings). A homozygous mutation within the informative LOH was found in three of these patients. Therefore, we were able to increase the diagnostic yield from 14.3% to 28.6% as a result of the information provided by LOHs., Conclusions: This study shows the clinical usefulness of SNP arrays in children with ID, since they successfully detect pathogenic CNVs, identify informative LOHs that can lead to the diagnosis of a recessive disorder. It also highlights some challenges associated with the use of SNP arrays in a clinical laboratory.

Published
2014
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31. Rare copy number variants contribute to congenital left-sided heart disease.

Author

Hitz MP, Lemieux-Perreault LP, Marshall C, Feroz-Zada Y, Davies R, Yang SW, Lionel AC, D'Amours G, Lemyre E, Cullum R, Bigras JL, Thibeault M, Chetaille P, Montpetit A, Khairy P, Overduin B, Klaassen S, Hoodless P, Awadalla P, Hussin J, Idaghdour Y, Nemer M, Stewart AF, Boerkoel C, Scherer SW, Richter A, Dubé MP, and Andelfinger G

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Animals, Child, Child, Preschool, Family, Female, Heart embryology, Humans, Male, Mice, Middle Aged, Myocardium metabolism, Neovascularization, Physiologic, Young Adult, DNA Copy Number Variations, Heart Defects, Congenital genetics
Abstract

Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology., Competing Interests: The authors have declared that no competing interests exist.

Published
2012
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32. Differential gene expression profiling in the mouse brain during motor skill learning: focus on the striatum structure.

Author

D'Amours G, Bureau G, Boily MJ, and Cyr M

Subjects
Animals, Cerebellum metabolism, Cerebellum physiology, Cerebral Cortex metabolism, Cerebral Cortex physiology, Corpus Striatum physiology, Male, Memory physiology, Mice, Mice, Inbred C57BL, Rotarod Performance Test methods, Corpus Striatum metabolism, Gene Expression Profiling methods, Learning physiology, Motor Skills physiology, Neuronal Plasticity genetics
Abstract

Much research has implicated the striatum in motor learning, but the underlying mechanism is still under extensive investigation. In this study, genome-wide analysis of gene expression was conducted in mice that have learned a complex motor task. It is well recognized that successful learning requires repetitive training and is learned slowly over several training sessions. We therefore used mice that have fully learned the accelerating rotarod task that discriminates the faster and slower phases of motor learning. As important modulators of movement behavior, the striatum was the target of this analysis along with the cerebellum and anterior cortex. To identify potential genes implicated in long memorization process, we compared the lists of genes modulated in the striatum to those modulated in the cerebellum and cortex. As a second approach, we also determined which gene ontology categories were enriched in modulated striatal genes and identified genes with the highest numbers of annotation throughout categories. Although only some of these changes were further confirmed by RT-PCR, these two complementary analyses allowed the identification of highly relevant genes like calcium/calmodulin-dependent protein kinase 2, protein kinase C zeta and N-methyl-D-aspartate receptors. Notably, these genes are all associated with synaptic plasticity, suggesting that stabilized neuronal connections in the striatum are the foundation of durable motor memory. Our study provides the first report of a whole genome analysis of gene expression in mice that have memorized a new complex motor task, and expands our knowledge on striatal gene expression changes associated with motor skill learning., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Published
2011
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