13 results on '"Tempia-Caliera, Michela"'
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2. Impact of Overweight and Obesity on Disease Outcome in the Pediatric Swiss Inflammatory Bowel Disease Cohort
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von Graffenried, Thea, Schoepfer, Alain M., Rossel, Jean-Benoit, Greuter, Thomas, Safroneeva, Ekaterina, Godat, Sébastien, Henchoz, Sarah, Vavricka, Stephan R., Sokollik, Christiane, Spalinger, Johannes, Braegger, Christian P., Nydegger, Andreas, Abdelrahman, Karim, Ademi, Gentiana, Aepli, Patrick, Thomas, Amman, Anderegg, Claudia, Antonino, Anca-Teodora, Archanioti, Eva, Arrigoni, Eviano, de Jong, Diana Bakker, Balsiger, Bruno, Bastürk, Polat, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Bengoa, José M., Biedermann, Luc, Binek, Janek, Blattmann, Mirjam, Boehm, Stephan, Boldanova, Tujana, Borovicka, Jan, Braegger, Christian P., Brand, Stephan, Brügger, Lukas, Brunner, Simon, Bühr, Patrick, Burnand, Bernard, Burk, Sabine, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, Carstens, Ove, Criblez, Dominique H., Cunningham, Sophie, D’Angelo, Fabrizia, de Saussure, Philippe, Degen, Lukas, Delarive, Joakim, Doerig, Christopher, Dora, Barbara, Drerup, Susan, Egger, Mara, El-Wafa, Ali, Engelmann, Matthias, Felley, Christian, Fliegner, Markus, Fournier, Nicolas, Fraga, Montserrat, Franc, Yannick, Frei, Pascal, Frei, Remus, Fried, Michael, Froehlich, Florian, Furlano, Raoul Ivano, Garzoni, Luca, Geyer, Martin, Girard, Laurent, Girardin, Marc, Golay, Delphine, Good, Ignaz, Bigler, Ulrike Graf, Gysi, Beat, Haarer, Johannes, Halama, Marcel, Haldemann, Janine, Heer, Pius, Heimgartner, Benjamin, Helbling, Beat, Hengstler, Peter, Herzog, Denise, Hess, Cyrill, Heyland, Klaas, Hinterleitner, Thomas, Hirschi, Claudia, Hruz, Petr, Juillerat, Pascal, Khalid-de Bakker, Carolina, Kayser, Stephan, Keller, Céline, Knellwolf, Christina, Knoblauch, Christoph, Köhler, Henrik, Koller, Rebekka, Krieger, Claudia, Künzler, Patrizia, Kusche, Rachel, Lehmann, Frank Serge, Macpherson, Andrew, Maillard, Michel H., Manz, Michael, Marot, Astrid, Meier, Rémy, Meyenberger, Christa, Meyer, Pamela, Michetti, Pierre, Misselwitz, Benjamin, Mosler, Patrick, Mottet, Christian, Müller, Christoph, Müllhaupt, Beat, Musso, Leilla, Neagu, Michaela, Nichita, Cristina, Niess, Jan, Nydegger, Andreas, Obialo, Nicole, Ollo, Diana, Oropesa, Cassandra, Peter, Ulrich, Peternac, Daniel, Petit, Laetitia Marie, Pittet, Valérie, Pohl, Daniel, Porzner, Marc, Preissler, Claudia, Raschle, Nadia, Rentsch, Ronald, Restellini, Alexandre, Restellini, Sophie, Richterich, Jean-Pierre, Ris, Frederic, Risti, Branislav, Ritz, Marc Alain, Rogler, Gerhard, Röhrich, Nina, Rossel, Jean-Benoît, Rueger, Vanessa, Rusticeanu, Monica, Sagmeister, Markus, Saner, Gaby, Sauter, Bernhard, Sawatzki, Mikael, Scharl, Michael, Schelling, Martin, Schibli, Susanne, Schlauri, Hugo, Schluckebier, Dominique, Schmid, Daniela, Schmid, Sybille, Schnegg, Jean-François, Schoepfer, Alain, Seematter, Vivianne, Seibold, Frank, Seirafi, Mariam, Semadeni, Gian-Marco, Senning, Arne, Sokollik, Christiane, Sommer, Joachim, Spalinger, Johannes, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Staudenmann, Dominic, Stenz, Volker, Steuerwald, Michael, Straumann, Alex, Stulz, Andreas, Sulz, Michael, Tatu, Aurora, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Tutuian, Radu, Urfer, Patrick, Vavricka, Stephan, Viani, Francesco, Vögtlin, Jürg, Von Känel, Roland, Vouillamoz, Dominique, Vulliamy, Rachel, Wiesel, Paul, Wiest, Reiner, Wöhrle, Stefanie, Zamora, Samuel, Zander, Silvan, Zeitz, Jonas, and Zimmermann, Dorothee
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- 2022
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3. The Incidence and Characteristics of Venous Thromboembolisms in Paediatric-Onset Inflammatory Bowel Disease:A Prospective International Cohort Study Based on the PIBD-SETQuality Safety Registry
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Aardoom, Martine A., Klomberg, Renz C.W., Kemos, Polychronis, Ruemmele, Frank M., Fagbemi, Andrew, Kiparissi, Fevronia, Schweizer, Joachim J., Sebastian, Shaji, Russell, Richard, Torrente, Franco, Van Mill, Marije, De Ridder, Lissy, Croft, Nicholas, Tempia-Caliera, Michela, Lee, Way Seah, Pigott, Anna J., Classen, Martin, Morris, Mary Anne, Muhammed, Rafeeq, Hussey, Seamus, Cananzi, Mara, Menz, Timothy J., Wahbeh, Ghassan T., Van Ommen, C. H.Heleen, Turner, Dan, Focht, Gili, Samsom, Janneke, Veereman, Gigi, Neyt, Mattias, Koletzko, Sibylle, Brückner, Annecarin, Levine, Arie, Weiner, Dror, Griffiths, Anne, Aloi, Marina, Raes, Jeroen, Christiaens, Annick, Walters, Thomas, Walker, Michael, Ruemelle, Frank, Demange, Christine Nguyen, Bigot, Laetitia, Aardoom, Martine A., Klomberg, Renz C.W., Kemos, Polychronis, Ruemmele, Frank M., Fagbemi, Andrew, Kiparissi, Fevronia, Schweizer, Joachim J., Sebastian, Shaji, Russell, Richard, Torrente, Franco, Van Mill, Marije, De Ridder, Lissy, Croft, Nicholas, Tempia-Caliera, Michela, Lee, Way Seah, Pigott, Anna J., Classen, Martin, Morris, Mary Anne, Muhammed, Rafeeq, Hussey, Seamus, Cananzi, Mara, Menz, Timothy J., Wahbeh, Ghassan T., Van Ommen, C. H.Heleen, Turner, Dan, Focht, Gili, Samsom, Janneke, Veereman, Gigi, Neyt, Mattias, Koletzko, Sibylle, Brückner, Annecarin, Levine, Arie, Weiner, Dror, Griffiths, Anne, Aloi, Marina, Raes, Jeroen, Christiaens, Annick, Walters, Thomas, Walker, Michael, Ruemelle, Frank, Demange, Christine Nguyen, and Bigot, Laetitia
- Abstract
Background and Aims: Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors. Methods: From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. IBD details [type, Paris classification, clinical and biochemical disease activity, treatment] and VTE details [type, location, treatment, outcome] were collected. To estimate VTE incidence, participants annually reported the number of PIBD patients, data source and catchment area of their centre. A systematic literature review and meta-analysis was performed to calculate the VTE incidence in the general paediatric population. Results: Participation of 129 PIBD centres resulted in coverage of 24 802 PIBD patients. Twenty cases of VTE were identified [30% Crohn's disease]. The incidence of VTEs was 3.72 (95% confidence interval [CI] 2.27-5.74) per 10 000 person-years, 14-fold higher than in the general paediatric population (0.27 [95% CI 0.18-0.38], p < 0.001). Cerebral sinus venous thrombosis was most frequently reported [50%]. All but one patient had active IBD, 45% were using steroids and 45% were hospitalized. No patient received thromboprophylaxis, whereas according to current PIBD guidelines, this was recommended in 4/20 patients. Conclusion: There is an increased risk of VTEs in the PIBD population compared to the general paediatric population. Awareness of VTE occurrence and prevention should be extended to all PIBD patients with active disease, especially those hospitalized.
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- 2022
4. The Incidence and Characteristics of Venous Thromboembolisms in Paediatric-Onset Inflammatory Bowel Disease: A Prospective International Cohort Study Based on the PIBD-SETQuality Safety Registry
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Aardoom, Martine A., Klomberg, Renz C.W., Kemos, Polychronis, Ruemmele, Frank M., Fagbemi, Andrew, Kiparissi, Fevronia, Schweizer, Joachim J., Sebastian, Shaji, Russell, Richard, Torrente, Franco, Van Mill, Marije, De Ridder, Lissy, Croft, Nicholas, Tempia-Caliera, Michela, Lee, Way Seah, Pigott, Anna J., Classen, Martin, Morris, Mary Anne, Muhammed, Rafeeq, Hussey, Seamus, Cananzi, Mara, Menz, Timothy J., Wahbeh, Ghassan T., Van Ommen, C. H.Heleen, Turner, Dan, Focht, Gili, Samsom, Janneke, Veereman, Gigi, Neyt, Mattias, Koletzko, Sibylle, Brückner, Annecarin, Levine, Arie, Weiner, Dror, Griffiths, Anne, Aloi, Marina, Raes, Jeroen, Christiaens, Annick, Walters, Thomas, Walker, Michael, Ruemelle, Frank, Demange, Christine Nguyen, Bigot, Laetitia, and Pediatrics
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Pediatrics ,medicine.medical_specialty ,Population ,Disease ,Inflammatory bowel disease ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Prospective Studies ,Registries ,education ,Child ,Venous Thrombosis ,education.field_of_study ,Crohn's disease ,business.industry ,Incidence (epidemiology) ,Incidence ,Gastroenterology ,Anticoagulants ,General Medicine ,Venous Thromboembolism ,medicine.disease ,Inflammatory Bowel Diseases ,Ulcerative colitis ,3. Good health ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Complication ,business ,Cohort study - Abstract
Background and Aims Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors. Methods From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient Results Participation of 129 PIBD centres resulted in coverage of 24 802 PIBD patients. Twenty cases of VTE were identified [30% Crohn’s disease]. The incidence of VTEs was 3.72 (95% confidence interval [CI] 2.27–5.74) per 10 000 person-years, 14-fold higher than in the general paediatric population (0.27 [95% CI 0.18–0.38], p < 0.001). Cerebral sinus venous thrombosis was most frequently reported [50%]. All but one patient had active IBD, 45% were using steroids and 45% were hospitalized. No patient received thromboprophylaxis, whereas according to current PIBD guidelines, this was recommended in 4/20 patients. Conclusion There is an increased risk of VTEs in the PIBD population compared to the general paediatric population. Awareness of VTE occurrence and prevention should be extended to all PIBD patients with active disease, especially those hospitalized.
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- 2021
5. Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohnʼs disease
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Safroneeva, E., Vavricka, S. R., Fournier, N., Pittet, V., Peyrin-Biroulet, L., Straumann, A., Rogler, G., Schoepfer, A. M., Bauerfeind, Peter, Beglinger, Christoph, Begré, Stefan, Bengoa, José, Binek, Janek, Boller, Daniel, Borovicka, Jan, Braegger, Christian, Burnand, Bernard, Camara, Rafael, Criblez, Dominique, de Saussure, Philippe, Degen, Lukas, Delarive, Joakim, Ehmann, Tobias, Engelmann, Matthias, Wafa, Ali El, Felley, Christian, Frei, Alain, Frei, Remus, Fried, Michael, Friedt, Michael, Froehlich, Florian, Gallot-Lavallée, Suzanne, Gerlach, Tilman, Geyer, Martin, Girardin, Marc, Goetze, Oliver, Haack, Horst, Hediger, Serge, Hengstler, Peter, Heyland, Klaas, Janiak, Patrick, Juillerat, Pascal, Brondolo, Vera Kessler, Knoblauch, Christoph, Kullak-Ublick, Gerd A., Maillard, Michel, Manz, Michael, Marbet, Urs, Meier, Rémy, Meyenberger, Christa, Michetti, Pierre, Mottet, Christian, Müller, Christoph, Müllhaupt, Beat, Nicolet, Thierry, Nydegger, Andreas, Pache, Isabelle, Piccoli, Franziska, Pilz, Julia, Rentsch, Ronald, Rey, Jean-Pierre, Rihs, Silvia, Rogler, Daniela, Sagmeister, Markus, Sauter, Bernhard, Schaub, Niklaus, Schibli, Susanne, Seibold, Frank, Spalinger, Johannes, Stadler, Philippe, Steuerwald, Michael, Sul, Michael, Tempia-Caliera, Michela, Thorens, Joël, Vader, John-Paul, Vögtlin, Jürg, Von Känel, Roland, Wachter, Gert, Wermuth, Jürg, and Wiesel, Paul
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- 2015
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6. Effects of anti-TNF therapy and immunomodulators on anxiety and depressive symptoms in patients with inflammatory bowel disease: a 5-year analysis
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Siebenhüner, Alexander R., primary, Rossel, Jean-Benoît, additional, Schreiner, Philipp, additional, Butter, Matthias, additional, Greuter, Thomas, additional, Krupka, Niklas, additional, Jordi, Sebastian B. U., additional, Biedermann, Luc, additional, Rogler, Gerhard, additional, Misselwitz, Benjamin, additional, von Känel, Roland, additional, Abdelrahman, Karim, additional, Ademi, Gentiana, additional, Aepli, Patrick, additional, Thomas, Amman, additional, Anderegg, Claudia, additional, Antonino, Anca-Teodora, additional, Archanioti, Eva, additional, Arrigoni, Eviano, additional, Aslan, Nurullah, additional, Bakker de Jong, Diana, additional, Balsiger, Bruno, additional, Barry, Mamadou-Pathé, additional, Bastürk, Polat, additional, Bauerfeind, Peter, additional, Becocci, Andrea, additional, Bengoa, José M., additional, Binek, Janek, additional, Blattmann, Mirjam, additional, Boehm, Stephan, additional, Boldanova, Tujana, additional, Borovicka, Jan, additional, Braegger, Christian P., additional, Brand, Stephan, additional, Bravo, Francisco, additional, Brügger, Lukas, additional, Brunner, Simon, additional, Bühr, Patrick, additional, Burk, Sabine, additional, Burri, Emanuel, additional, Buyse, Sophie, additional, Cao, Dahlia-Thao, additional, Carstens, Ove, additional, Criblez, Dominique H., additional, D’Angelo, Fabrizia, additional, Saussure, Philippe de, additional, Degen, Lukas, additional, Delarive, Joakim, additional, Doerig, Christopher, additional, Dora, Barbara, additional, Drerup, Susan, additional, Ducrey, Carole, additional, El-Wafa, Ali, additional, Engelmann, Matthias, additional, Erdmann-Voisin, Aude, additional, Felley, Christian, additional, Fliegner, Markus, additional, Fraga, Montserrat, additional, Franc, Yannick, additional, Frei, Pascal, additional, Frei, Remus, additional, Fried, Michael, additional, Froehlich, Florian, additional, Ivano Furlano, Raoul, additional, Garzoni, Luca, additional, Geyer, Martin, additional, Girardin, Marc, additional, Golay, Delphine, additional, Good, Ignaz, additional, Graf Bigler, Ulrike, additional, Godat, Sébastien, additional, Gysi, Beat, additional, Haarer, Johannes, additional, Halama, Marcel, additional, Haldemann, Janine, additional, Heer, Pius, additional, Heimgartner, Benjamin, additional, Helbling, Beat, additional, Hengstler, Peter, additional, Herzog, Denise, additional, Hess, Cyrill, additional, Hessler, Roxane, additional, Heyland, Klaas, additional, Hinterleitner, Thomas, additional, Hirschi, Claudia, additional, Hruz, Petr, additional, Juillerat, Pascal, additional, Kapoglou, Ioannis, additional, Kayser, Stephan, additional, Keller, Céline, additional, Khalid-de Bakker, Carolina, additional, Knellwolf, Christina, additional, Knoblauch, Christoph, additional, Köhler, Henrik, additional, Koller, Rebekka, additional, Krieger, Claudia, additional, Künzler, Patrizia, additional, Kusche, Rachel, additional, Serge Lehmann, Frank, additional, Macpherson, Andrew, additional, Maillard, Michel H., additional, Manz, Michael, additional, Martinho, Maude, additional, Meier, Rémy, additional, Meyenberger, Christa, additional, Meyer, Pamela, additional, Michetti, Pierre, additional, Morell, Bernhard, additional, Mosler, Patrick, additional, Moschouri, Eleni, additional, Mottet, Christian, additional, Müller, Christoph, additional, Müllhaupt, Beat, additional, Musso, Leilla, additional, Neagu, Michaela, additional, Nichita, Cristina, additional, Niess, Jan, additional, Nydegger, Andreas, additional, Obialo, Nicole, additional, Oropesa, Cassandra, additional, Peter, Ulrich, additional, Peternac, Daniel, additional, Marie Petit, Laetitia, additional, Pittet, Valérie, additional, Pohl, Daniel, additional, Porzner, Marc, additional, Preissler, Claudia, additional, Raschle, Nadia, additional, Rentsch, Ronald, additional, Restellini, Sophie, additional, Richterich, Jean-Pierre, additional, Riedmüller, Sandra, additional, Risti, Branislav, additional, Alain Ritz, Marc, additional, Röhrich, Nina, additional, Roth, René, additional, Rueger, Vanessa, additional, Sagmeister, Markus, additional, Saner, Gaby, additional, Sarraj, Riad, additional, Sauter, Bernhard, additional, Sawatzki, Mikael, additional, Scharl, Michael, additional, Scharl, Sylvie, additional, Schelling, Martin, additional, Schibli, Susanne, additional, Schlauri, Hugo, additional, Schluckebier, Dominique, additional, Schmid, Daniela, additional, Schmid, Sybille, additional, Schnegg, Jean-François, additional, Schoepfer, Alain, additional, Seibold, Frank, additional, Seirafi, Mariam, additional, Semadeni, Gian-Marco, additional, Senning, Arne, additional, Sokollik, Christiane, additional, Sommer, Joachim, additional, Spalinger, Johannes, additional, Spangenberger, Holger, additional, Stadler, Philippe, additional, Staub, Peter, additional, Staudenmann, Dominic, additional, Stenz, Volker, additional, Steuerwald, Michael, additional, Straumann, Alex, additional, Stulz, Andreas, additional, Sulz, Michael, additional, Tempia-Caliera, Michela, additional, Thorens, Joël, additional, Truninger, Kaspar, additional, Tutuian, Radu, additional, Urfer, Patrick, additional, Vavricka, Stephan, additional, Viani, Francesco, additional, Vinzens, Fabrizion, additional, Vögtlin, Jürg, additional, Von Känel, Roland, additional, Vouillamoz, Dominique, additional, Vulliamy, Rachel, additional, Vullièmoz, Marianne, additional, Wiesel, Paul, additional, Wiest, Reiner, additional, Wöhrle, Stefanie, additional, Yilmaz, Bahtiyar, additional, Zamora, Samuel, additional, Zander, Silvan, additional, Zeitz, Jonas, additional, and Zimmermann, Dorothee, additional
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- 2021
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7. Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study
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Charbit-Henrion, Fabienne, primary, Parlato, Marianna, additional, Hanein, Sylvain, additional, Duclaux-Loras, Rémi, additional, Nowak, Jan, additional, Begue, Bernadette, additional, Rakotobe, Sabine, additional, Bruneau, Julie, additional, Fourrage, Cécile, additional, Alibeu, Olivier, additional, Rieux-Laucat, Frédéric, additional, Lévy, Eva, additional, Stolzenberg, Marie-Claude, additional, Mazerolles, Fabienne, additional, Latour, Sylvain, additional, Lenoir, Christelle, additional, Fischer, Alain, additional, Picard, Capucine, additional, Aloi, Marina, additional, Dias, Jorge Amil, additional, Hariz, Mongi Ben, additional, Bourrier, Anne, additional, Breuer, Christian, additional, Breton, Anne, additional, Bronsky, Jiri, additional, Buderus, Stephan, additional, Cananzi, Mara, additional, Coopman, Stéphanie, additional, Crémilleux, Clara, additional, Dabadie, Alain, additional, Dumant-Forest, Clémentine, additional, Gurkan, Odul Egritas, additional, Fabre, Alexandre, additional, Fischer, Aude, additional, Diaz, Marta German, additional, Gonzalez-Lama, Yago, additional, Goulet, Olivier, additional, Guariso, Graziella, additional, Gurcan, Neslihan, additional, Homan, Matjaz, additional, Hugot, Jean-Pierre, additional, Jeziorski, Eric, additional, Karanika, Evi, additional, Lachaux, Alain, additional, Lewindon, Peter, additional, Lima, Rosa, additional, Magro, Fernando, additional, Major, Janos, additional, Malamut, Georgia, additional, Mas, Emmanuel, additional, Mattyus, Istvan, additional, Mearin, Luisa M, additional, Melek, Jan, additional, Navas-Lopez, Victor Manuel, additional, Paerregaard, Anders, additional, Pelatan, Cecile, additional, Pigneur, Bénédicte, additional, Pais, Isabel Pinto, additional, Rebeuh, Julie, additional, Romano, Claudio, additional, Siala, Nadia, additional, Strisciuglio, Caterina, additional, Tempia-Caliera, Michela, additional, Tounian, Patrick, additional, Turner, Dan, additional, Urbonas, Vaidotas, additional, Willot, Stéphanie, additional, Ruemmele, Frank M, additional, and Cerf-Bensussan, Nadine, additional
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- 2020
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8. Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: A multicentre study
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Charbit-Henrion, Fabienne, Parlato, Marianna, Hanein, Sylvain, Duclaux-Loras, Remi, Nowak, Jan, Bègue, Bernadette, Rakotobe, Sabine, Bruneau, Julie, Fourrage, Cécile, Alibeu, Olivier, Rieux-Laucat, Frédéric, Lévy, Eva, Stolzenberg, Marie-Claude, Mazerolles, Fabienne, Latour, Sylvain, Lenoir, Christelle, Fischer, Alain, Picard, Capucine, Aloi, Marina, Amil Dias, Jorge, Ben Hariz, Mongi, Bourrier, Anne, Breuer, Christian, Breton, Anne, Bronski, Jiri, Buderus, Stephan, Cananzi, Mara, Coopman, Stéphanie, Crémilleux, Clara, Dabadie, Alain, Dumant-Forest, Clémentine, Egritas Gurkan, Odul, Fabre, Alexandre, Fischer, Aude, German Diaz, Marta, Gonzalez-Lama, Yago, Goulet, Olivier, Guariso, Graziella, Gurcan, Neslihan, Homan, Matjaz, Hugot, Jean-Pierre, Jeziorski, Eric, Karanika, Evi, Lachaux, Alain, Lewindon, Peter, Lima, Rosa, Magro, Fernando, Major, Janos, Malamut, Georgia, Mas, Emmanuel, Mattyus, Istvan, Mearin, Luisa, Melek, Jan, Navas-Lopez, Victor Manuel, Paerregaard, Anders, Pelatan, Cecile, Pigneur, Bénédicte, Pinto Pais, Isabel, Rebeuh, Julie, Romano, Claudio, Siala, Nadia, Strisciuglio, Caterina, Tempia-Caliera, Michela, Tounian, Patrick, Turner, Dan, Urbonas, Vaidotas, Willot, Stéphanie, Ruemmele, Frank, Cerf-Bensussan, Nadine, Charbit-Henrion, Fabienne, Parlato, Marianna, Hanein, Sylvain, Duclaux-Loras, Rémi, Nowak, Jan, Begue, Bernadette, Rakotobe, Sabine, Bruneau, Julie, Fourrage, Cécile, Alibeu, Olivier, Rieux-Laucat, Frédéric, Lévy, Eva, Stolzenberg, Marie-Claude, Mazerolles, Fabienne, Latour, Sylvain, Lenoir, Christelle, Fischer, Alain, Picard, Capucine, Aloi, Marina, Dias, Jorge Amil, Hariz, Mongi Ben, Bourrier, Anne, Breuer, Christian, Breton, Anne, Bronski, Jiri, Buderus, Stephan, Cananzi, Mara, Coopman, Stéphanie, Crémilleux, Clara, Dabadie, Alain, Dumant-Forest, Clémentine, Gurkan, Odul Egrita, Fabre, Alexandre, Fischer, Aude, Diaz, Marta German, Gonzalez-Lama, Yago, Goulet, Olivier, Guariso, Graziella, Gurcan, Neslihan, Homan, Matjaz, Hugot, Jean-Pierre, Jeziorski, Eric, Karanika, Evi, Lachaux, Alain, Lewindon, Peter, Lima, Rosa, Magro, Fernando, Major, Jano, Malamut, Georgia, Mas, Emmanuel, Mattyus, Istvan, Mearin, Luisa M, Melek, Jan, Navas-Lopez, Victor Manuel, Paerregaard, Ander, Pelatan, Cecile, Pigneur, Bénédicte, Pais, Isabel Pinto, Rebeuh, Julie, Romano, Claudio, Siala, Nadia, Strisciuglio, Caterina, Tempia-Caliera, Michela, Tounian, Patrick, Turner, Dan, Urbonas, Vaidota, Willot, Stéphanie, Ruemmele, Frank M., Cerf-Bensussan, Nadine, Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), The Clinical Bioinformatics laboratory (Equipe Inserm U1163), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), GENIUS Group, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pédiatrie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Gastroentérologie-Hépatologie et Nutrition Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Hospital de São João [Porto], Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Le Mans (CH Le Mans), University of Messina, Department of Pediatrics, Centre Hospitalier Universitaire Mongi Slim [La Marsa], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Gastroentérologie, d'hépatologie et nutrition pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), CHU Le MAns, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,paediatric ,VEO-IBD ,Adolescent ,monogenic disorder ,Gastroenterology ,High-Throughput Nucleotide Sequencing ,Infant ,Genetics and molecular epidemiology ,Inflammatory Bowel Diseases ,monogenic disorders ,Corrigenda ,Cohort Studies ,paediatrics ,Predictive Value of Tests ,Child, Preschool ,TNGS ,Humans ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Age of Onset ,Child ,Genetics and molecular epidemiology, monogenic disorders, paediatrics, TNGS, VEO-IBD, Gastroenterology ,AcademicSubjects/MED00260 - Abstract
Background and Aims An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: Predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.
- Published
- 2018
9. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
- Author
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Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M., Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K., Barakat, Farah, Auth, Marcus K. H., Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P., Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C., Gilmour, Kimberly C., Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A., Fulga, Tudor A., Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C., Elkadri, Abdul, Griffiths, Anne M., Snapper, Scott B., Shah, Neil, Muise, Aleixo M., Wilson, David C., Uhlig, Holm H., Anderson, Carl A., Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Arancibia-Carcamo, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Elizabeth Louise, Brain, Oliver, Braden, Barbara, Collier, Jane, East, James, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Powrie, Fiona, Simmons, Alison, Walker, Matthew, Tolkien, Zoe, Kaptoge, Stephen, Allen, David, Mehenny, Susan, Mant, Jonathan, Di Angelantonio, Emanuele, Thompson, Simon G., Yilmaz, Bahtiyar, Juillerat, Pascal, Geuking, Markus, Wiest, Reiner, Macpherson, Andrew J., Bravo, Francisco Damian, Brügger, Lukas, Carstens, Ove, Bigler, Ulrike Graf, Heimgartner, Benjamin, Rusticeanu, Monica, Schmid (-Uebelhart), Sybille, Strebel, Bruno, Tatu, Aurora, Tutuian, Radu, Øyås, Ove, Ramon, Charlotte, Stelling, Jörg, Franc, Yannick, Fournier, Nicolas, Pittet, Valerie E. H., Burnand, Bernard, Egger, Mara, Golay, Delphine, Marot, Astrid, Musso, Leilla, Pittet, Valérie, Rossel, Jean-Benoît, Seematter, Vivianne, Sommer, Joachim, Vulliamy, Rachel, Michetti, Pierre, Maillard, Michel H., Keller, Céline, Nydegger, Andreas, Schoepfe, Alain, Archanioti, Eva, Ezri, Jessica, Fraga, Montserrat, Schoepfer, Alain, Müller, Christoph, Rogler, Gerhard, Biedermann, Luc, Blattmann, Mirjam, Burk, Sabine, Dora, Barbara, Fried, Michael, Misselwitz, Benjamin, Müllhaupt, Beat, Obialo, Nicole, Pohl, Daniel, Raschle, Nadia, Scharl, Michael, Vavricka, Stephan, Von Känel, Roland, Zeitz, Jonas, Abdelrahman, Karim, Ademi, Gentiana, Borovicka, Jan, Brand, Stephan, Frei, Remus, Haarer, Johannes, Knellwolf (-Grieger), Christina, Krieger(-Grübel), Claudia, Künzler, Patrizia, Meyenberger, Christa, Meyer, Pamela, Röhrich, Nina, Sawatzki, Mikael, Schelling, Martin, Semadeni, Gian-Marco, Sulz, Michael, Zimmermann, Dorothee, Aepli, Patrick, Criblez, Dominique H., Hess, Cyrill, Richterich, Jean-Pierre, Spalinger, Johannes, Staudenmann, Dominic, Stulz, Andreas, Wöhrle, Stefanie, Thomas, Amman, Anderegg, Claudia, Köhler, Henrik, Kusche, Rachel, Antonino, Anca-Teodora, Arrigoni, Eviano, Bengoa, José M., Cunningham, Sophie, De Saussure, Philippe, Girard, Laurent, De Jong, Diana Bakker, Bastürk, Polat, Brunner, Simon, Degen, Lukas, Hruz, Petr, Bakker, Carolina Khalid-De, Niess, Jan, Balsiger, Bruno, Haldemann, Janine, Saner, Gaby, Seibold, Frank, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Binek, Janek, Hengstler, Peter, Boehm, Stephan, Boldanov, Tujana, Bühr, Patrick, Koller, Rebekka, Rueger, Vanessa, Senning, Arne, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, D’Angelo, Fabrizia, Delarive, Joakim, Doerig, Christopher, Hessler, Roxane, Preissler, Claudia, Rentsch, Ronald, Risti, Branislav, Ritz, Marc Alain, Steuerwald, Michael, Vögtlin, Jürg, Sagmeister, Markus, Sauter, Bernhard, Schibli, Susanne, Sokollik, Christiane, Schlauri, Hugo, Schnegg, Jean-François, Seirafi, Mariam, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Stenz, Volker, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Urfer, Patrick, Viani, Francesco, Vouillamoz, Dominique, Zander, Silvan, Wyli, Tina, Jostins, L., Kennedy, N. A., Ahmad, T., Lamb, C. A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Mathew, C. G., Lees, C. W., McGovern, D. P. B., Targan, S. R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J. D., Bitton, A., Côté-Daigneault, J., Daly, M. J., Xavier, R., Morris, K., Boucher, G., Cho, J. H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R. H., Konnikova, L., Schwartz, M. B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S. R., Datta, L., Silverberg, M. S., Schumm, L. P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., and Haritunians, T.
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49/31 ,45 ,article ,45/22 ,631/208/1516 ,692/699/249/1570 ,45/23 ,631/250/249/2510/257 ,631/208/248 ,13 ,digestive system diseases ,3. Good health ,49 - Abstract
Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.
10. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
- Author
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Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, Marlen, Zurek, Caterina, Strisciuglio, Mamoun, Elawad, Bernice, Lo, Carolina, Arancibia-Carcamo, Adam, Bailey, Ellie, Barnes, Elizabeth Louise, Bird-Lieberman, Oliver, Brain, Barbara, Braden, Jane, Collier, James, East, Lucy, Howarth, Satish, Keshav, Paul, Klenerman, Simon, Leedham, Rebecca, Palmer, Fiona, Powrie, Alison, Simmons, Matthew, Walker, Zoe, Tolkien, Stephen, Kaptoge, David, Allen, Susan, Mehenny, Jonathan, Mant, Emanuele, Di Angelantonio, Simon G, Thompson, Bahtiyar, Yilmaz, Pascal, Juillerat, Markus, Geuking, Reiner, Wiest, Andrew J, Macpherson, Francisco Damian, Bravo, Lukas, Brügger, Ove, Carstens, Ulrike Graf, Bigler, Benjamin, Heimgartner, Monica, Rusticeanu, Sybille, Schmid-Uebelhart, Bruno, Strebel, Aurora, Tatu, Radu, Tutuian, Ove, Øyås, Charlotte, Ramon, Jörg, Stelling, Yannick, Franc, Nicolas, Fournier, Valerie E H, Pittet, Bernard, Burnand, Mara, Egger, Delphine, Golay, Astrid, Marot, Leilla, Musso, Valérie, Pittet, Jean-Benoît, Rossel, Vivianne, Seematter, Joachim, Sommer, Rachel, Vulliamy, Pierre, Michetti, Michel H, Maillard, Céline, Keller, Andreas, Nydegger, Alain, Schoepfe, Eva, Archanioti, Jessica, Ezri, Montserrat, Fraga, Alain, Schoepfer, Christoph, Müller, Gerhard, Rogler, Luc, Biedermann, Mirjam, Blattmann, Sabine, Burk, Barbara, Dora, Michael, Fried, Benjamin, Misselwitz, Beat, Müllhaupt, Nicole, Obialo, Daniel, Pohl, Nadia, Raschle, Michael, Scharl, Stephan, Vavricka, Roland, Von Känel, Jonas, Zeitz, Karim, Abdelrahman, Gentiana, Ademi, Jan, Borovicka, Stephan, Brand, Remus, Frei, Johannes, Haarer, Christina, Knellwolf-Grieger, Claudia, Krieger-Grübel, Patrizia, Künzler, Christa, Meyenberger, Pamela, Meyer, Nina, Röhrich, Mikael, Sawatzki, Martin, Schelling, Gian-Marco, Semadeni, Michael, Sulz, Dorothee, Zimmermann, Patrick, Aepli, Dominique H, Criblez, Cyrill, Hess, Jean-Pierre, Richterich, Johannes, Spalinger, Dominic, Staudenmann, Andreas, Stulz, Stefanie, Wöhrle, Amman, Thomas, Claudia, Anderegg, Henrik, Köhler, Rachel, Kusche, Anca-Teodora, Antonino, Eviano, Arrigoni, José M, Bengoa, Sophie, Cunningham, Philippe, de Saussure, Laurent, Girard, Diana Bakker, de Jong, Polat, Bastürk, Simon, Brunner, Lukas, Degen, Petr, Hruz, Carolina, Khalid-de Bakker, Jan, Niess, Bruno, Balsiger, Janine, Haldemann, Gaby, Saner, Frank, Seibold, Peter, Bauerfeind, Andrea, Becocci, Dominique, Belli, Janek, Binek, Peter, Hengstler, Stephan, Boehm, Tujana, Boldanov, Patrick, Bühr, Rebekka, Koller, Vanessa, Rueger, Arne, Senning, Emanuel, Burri, Sophie, Buyse, Dahlia-Thao, Cao, Fabrizia, D'Angelo, Joakim, Delarive, Christopher, Doerig, Roxane, Hessler, Claudia, Preissler, Ronald, Rentsch, Branislav, Risti, Marc Alain, Ritz, Michael, Steuerwald, Jürg, Vögtlin, Markus, Sagmeister, Bernhard, Sauter, Susanne, Schibli, Christiane, Sokollik, Hugo, Schlauri, Jean-François, Schnegg, Mariam, Seirafi, Holger, Spangenberger, Philippe, Stadler, Peter, Staub, Volker, Stenz, Michela, Tempia-Caliera, Joël, Thorens, Kaspar, Truninger, Patrick, Urfer, Francesco, Viani, Dominique, Vouillamoz, Silvan, Zander, Tina, Wyli, L, Jostins, N A, Kennedy, T, Ahmad, C A, Lamb, C, Edwards, A, Hart, C, Hawkey, J C, Mansfield, C, Mowat, W G, Newman, A, Simmons, M, Tremelling, J C, Lee, N J, Prescott, C G, Mathew, C W, Lees, D P B, McGovern, S R, Targan, G, Botwin, E, Mengesha, P, Fleshner, C, Landers, D, Li, J D, Rioux, A, Bitton, J, Côté-Daigneault, M J, Daly, R, Xavier, K, Morris, G, Boucher, J H, Cho, C, Abraham, M, Merad, B, Sands, I, Peter, K, Hao, Y, Itan, R H, Duerr, L, Konnikova, M B, Schwartz, S, Proksell, E, Johnston, V, Miladinova, W, Chen, S R, Brant, L, Datta, M S, Silverberg, L P, Schumm, S, Birch, M, Giri, K, Gettler, Y, Sharma, C, Stevens, M, Lazarev, T, Haritunians, Fachal, Laura [0000-0002-7256-9752], Croft, Nicholas M [0000-0002-1519-6435], Posovszky, Carsten [0000-0002-9487-8812], Russell, Richard K [0000-0001-7398-4926], Zilbauer, Matthias [0000-0002-7272-0547], Travis, Simon P [0000-0002-2690-4361], Matte, Julie C [0000-0001-5642-648X], Wedrychowicz, Andrzej [0000-0003-1448-167X], Fulga, Tudor A [0000-0002-1056-0082], Karaminejadranjbar, Mohammad [0000-0002-7770-2065], Ahmed, Ahmed [0000-0001-6509-2581], Muise, Aleixo M [0000-0001-9624-3346], Wilson, David C [0000-0003-0879-1129], Apollo - University of Cambridge Repository, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Croft, Nicholas M. [0000-0002-1519-6435], Russell, Richard K. [0000-0001-7398-4926], Travis, Simon P. [0000-0002-2690-4361], Matte, Julie C. [0000-0001-5642-648X], Fulga, Tudor A. [0000-0002-1056-0082], Muise, Aleixo M. [0000-0001-9624-3346], Wilson, David C. [0000-0003-0879-1129], Eva Gonçalves, Serra, Tobias, Schwerd, Loukas, Moutsiana, Athena, Cavounidi, Laura, Fachal, Sumeet, Pandey, Jochen, Kammermeier, Nicholas M, Croft, Carsten, Posovszky, Astor, Rodrigue, Richard K, Russell, Farah, Barakat, Marcus K H, Auth, Robert, Heuschkel, Matthias, Zilbauer, Krzysztof, Fyderek, Christian, Braegger, Simon P, Travi, Jack, Satsangi, Miles, Parke, Nikhil, Thapar, Helen, Ferry, Julie C, Matte, Kimberly C, Gilmour, Andrzej, Wedrychowicz, Peter, Sullivan, Carmel, Moore, Jennifer, Sambrook, Willem, Ouwehand, David, Robert, John, Danesh, Toni A, Baeumler, Tudor A, Fulga, Mohammad, Karaminejadranjbar, Ahmed, Ahmed, Rachel, Wilson, Jeffrey C, Barrett, Abdul, Elkadri, Anne M, Griffith, Scott B, Snapper, Neil, Shah, Aleixo M, Muise, David C, Wilson, Holm H, Uhlig, Carl A, Anderson, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Arancibia-Carcamo, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Elizabeth Louise, Brain, Oliver, Braden, Barbara, Collier, Jane, East, Jame, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Powrie, Fiona, Simmons, Alison, Walker, Matthew, Tolkien, Zoe, Kaptoge, Stephen, Allen, David, Mehenny, Susan, Mant, Jonathan, Di Angelantonio, Emanuele, Thompson, Simon G, Yilmaz, Bahtiyar, Juillerat, Pascal, Geuking, Marku, Wiest, Reiner, Macpherson, Andrew J, Bravo, Francisco Damian, Brügger, Luka, Carstens, Ove, Bigler, Ulrike Graf, Heimgartner, Benjamin, Rusticeanu, Monica, Schmid-Uebelhart, Sybille, Strebel, Bruno, Tatu, Aurora, Tutuian, Radu, Øyås, Ove, Ramon, Charlotte, Stelling, Jörg, Franc, Yannick, Fournier, Nicola, Pittet, Valerie E H, Burnand, Bernard, Egger, Mara, Golay, Delphine, Marot, Astrid, Musso, Leilla, Pittet, Valérie, Rossel, Jean-Benoît, Seematter, Vivianne, Sommer, Joachim, Vulliamy, Rachel, Michetti, Pierre, Maillard, Michel H, Keller, Céline, Nydegger, Andrea, Schoepfe, Alain, Archanioti, Eva, Ezri, Jessica, Fraga, Montserrat, Schoepfer, Alain, Müller, Christoph, Rogler, Gerhard, Biedermann, Luc, Blattmann, Mirjam, Burk, Sabine, Dora, Barbara, Fried, Michael, Misselwitz, Benjamin, Müllhaupt, Beat, Obialo, Nicole, Pohl, Daniel, Raschle, Nadia, Scharl, Michael, Vavricka, Stephan, Von Känel, Roland, Zeitz, Jona, Abdelrahman, Karim, Ademi, Gentiana, Borovicka, Jan, Brand, Stephan, Frei, Remu, Haarer, Johanne, Knellwolf-Grieger, Christina, Krieger-Grübel, Claudia, Künzler, Patrizia, Meyenberger, Christa, Meyer, Pamela, Röhrich, Nina, Sawatzki, Mikael, Schelling, Martin, Semadeni, Gian-Marco, Sulz, Michael, Zimmermann, Dorothee, Aepli, Patrick, Criblez, Dominique H, Hess, Cyrill, Richterich, Jean-Pierre, Spalinger, Johanne, Staudenmann, Dominic, Stulz, Andrea, Wöhrle, Stefanie, Thomas, Amman, Anderegg, Claudia, Köhler, Henrik, Kusche, Rachel, Antonino, Anca-Teodora, Arrigoni, Eviano, Bengoa, José M, Cunningham, Sophie, de Saussure, Philippe, Girard, Laurent, de Jong, Diana Bakker, Bastürk, Polat, Brunner, Simon, Degen, Luka, Hruz, Petr, Khalid-de Bakker, Carolina, Niess, Jan, Balsiger, Bruno, Haldemann, Janine, Saner, Gaby, Seibold, Frank, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Binek, Janek, Hengstler, Peter, Boehm, Stephan, Boldanov, Tujana, Bühr, Patrick, Koller, Rebekka, Rueger, Vanessa, Senning, Arne, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, D'Angelo, Fabrizia, Delarive, Joakim, Doerig, Christopher, Hessler, Roxane, Preissler, Claudia, Rentsch, Ronald, Risti, Branislav, Ritz, Marc Alain, Steuerwald, Michael, Vögtlin, Jürg, Sagmeister, Marku, Sauter, Bernhard, Schibli, Susanne, Sokollik, Christiane, Schlauri, Hugo, Schnegg, Jean-Françoi, Seirafi, Mariam, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Stenz, Volker, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Urfer, Patrick, Viani, Francesco, Vouillamoz, Dominique, Zander, Silvan, Wyli, Tina, Jostins, L, Kennedy, N A, Ahmad, T, Lamb, C A, Edwards, C, Hart, A, Hawkey, C, Mansfield, J C, Mowat, C, Newman, W G, Simmons, A, Tremelling, M, Lee, J C, Prescott, N J, Mathew, C G, Lees, C W, Mcgovern, D P B, Targan, S R, Botwin, G, Mengesha, E, Fleshner, P, Landers, C, Li, D, Rioux, J D, Bitton, A, Côté-Daigneault, J, Daly, M J, Xavier, R, Morris, K, Boucher, G, Cho, J H, Abraham, C, Merad, M, Sands, B, Peter, I, Hao, K, Itan, Y, Duerr, R H, Konnikova, L, Schwartz, M B, Proksell, S, Johnston, E, Miladinova, V, Chen, W, Brant, S R, Datta, L, Silverberg, M S, Schumm, L P, Birch, S, Giri, M, Gettler, K, Sharma, Y, Stevens, C, Lazarev, M, Haritunians, T, Carrami, Eli M [0000-0002-7770-2065], COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, Zurek, M., Strisciuglio, C., Elawad, M., Lo, B., Arancibia-Carcamo, C., Bailey, A., Barnes, E., Bird-Lieberman, E.L., Brain, O., Braden, B., Collier, J., East, J., Howarth, L., Keshav, S., Klenerman, P., Leedham, S., Palmer, R., Powrie, F., Simmons, A., Walker, M., Tolkien, Z., Kaptoge, S., Allen, D., Mehenny, S., Mant, J., Di Angelantonio, E., Thompson, S.G., Yilmaz, B., Juillerat, P., Geuking, M., Wiest, R., Macpherson, A.J., Bravo, F.D., Brügger, L., Carstens, O., Bigler, U.G., Heimgartner, B., Rusticeanu, M., Schmid-Uebelhart, S., Strebel, B., Tatu, A., Tutuian, R., Øyås, O., Ramon, C., Stelling, J., Franc, Y., Fournier, N., Pittet, VEH, Burnand, B., Egger, M., Golay, D., Marot, A., Musso, L., Pittet, V., Rossel, J.B., Seematter, V., Sommer, J., Vulliamy, R., Michetti, P., Maillard, M.H., Keller, C., Nydegger, A., Schoepfe, A., Archanioti, E., Ezri, J., Fraga, M., Schoepfer, A., Müller, C., Rogler, G., Biedermann, L., Blattmann, M., Burk, S., Dora, B., Fried, M., Misselwitz, B., Müllhaupt, B., Obialo, N., Pohl, D., Raschle, N., Scharl, M., Vavricka, S., Von Känel, R., Zeitz, J., Abdelrahman, K., Ademi, G., Borovicka, J., Brand, S., Frei, R., Haarer, J., Knellwolf-Grieger, C., Krieger-Grübel, C., Künzler, P., Meyenberger, C., Meyer, P., Röhrich, N., Sawatzki, M., Schelling, M., Semadeni, G.M., Sulz, M., Zimmermann, D., Aepli, P., Criblez, D.H., Hess, C., Richterich, J.P., Spalinger, J., Staudenmann, D., Stulz, A., Wöhrle, S., Thomas, A., Anderegg, C., Köhler, H., Kusche, R., Antonino, A.T., Arrigoni, E., Bengoa, J.M., Cunningham, S., de Saussure, P., Girard, L., de Jong, D.B., Bastürk, P., Brunner, S., Degen, L., Hruz, P., Bakker, C.K., Niess, J., Balsiger, B., Haldemann, J., Saner, G., Seibold, F., Bauerfeind, P., Becocci, A., Belli, D., Binek, J., Hengstler, P., Boehm, S., Boldanov, T., Bühr, P., Koller, R., Rueger, V., Senning, A., Burri, E., Buyse, S., Cao, D.T., D'Angelo, F., Delarive, J., Doerig, C., Hessler, R., Preissler, C., Rentsch, R., Risti, B., Ritz, M.A., Steuerwald, M., Vögtlin, J., Sagmeister, M., Sauter, B., Schibli, S., Sokollik, C., Schlauri, H., Schnegg, J.F., Seirafi, M., Spangenberger, H., Stadler, P., Staub, P., Stenz, V., Tempia-Caliera, M., Thorens, J., Truninger, K., Urfer, P., Viani, F., Vouillamoz, D., Zander, S., Wyli, T., Jostins, L., Kennedy, N.A., Ahmad, T., Lamb, C.A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J.C., Mowat, C., Newman, W.G., Tremelling, M., Lee, J.C., Prescott, N.J., Mathew, C.G., Lees, C.W., McGovern, DPB, Targan, S.R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J.D., Bitton, A., Côté-Daigneault, J., Daly, M.J., Xavier, R., Morris, K., Boucher, G., Cho, J.H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R.H., Konnikova, L., Schwartz, M.B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S.R., Datta, L., Silverberg, M.S., Schumm, L.P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., and Haritunians, T.
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0301 basic medicine ,Male ,Multifactorial Inheritance ,General Physics and Astronomy ,631/208/1516 ,13 ,Inflammatory bowel disease ,Whole Exome Sequencing ,Adult ,Age of Onset ,Case-Control Studies ,Child ,Child, Preschool ,Cohort Studies ,Female ,Genes, Recessive ,Genetic Predisposition to Disease ,Genetic Variation ,Humans ,Infant ,Infant, Newborn ,Inflammatory Bowel Diseases/etiology ,Inflammatory Bowel Diseases/genetics ,Loss of Function Mutation ,Mosaicism ,Mutation ,NADPH Oxidase 2/genetics ,Pedigree ,Primary Immunodeficiency Diseases/complications ,Primary Immunodeficiency Diseases/genetics ,Risk Factors ,0302 clinical medicine ,Primary Immunodeficiency Disease ,Medicine ,lcsh:Science ,Exome sequencing ,49/31 ,education.field_of_study ,Multidisciplinary ,Medical genetics ,article ,692/699/249/1570 ,631/250/249/2510/257 ,631/208/248 ,3. Good health ,NADPH Oxidase 2 ,030211 gastroenterology & hepatology ,Case-Control Studie ,Human ,medicine.medical_specialty ,Science ,Primary Immunodeficiency Diseases ,Population ,45/22 ,45/23 ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immunological deficiency syndromes ,Exome Sequencing ,Immunogenetics ,Allele ,education ,45 ,business.industry ,Risk Factor ,Inflammatory Bowel Disease ,Case-control study ,General Chemistry ,medicine.disease ,Inflammatory Bowel Diseases ,digestive system diseases ,49 ,030104 developmental biology ,Immunology ,Primary immunodeficiency ,lcsh:Q ,Age of onset ,Cohort Studie ,business - Abstract
Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P, Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.
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- 2020
11. Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study
- Author
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Olivier Alibeu, P. Tounian, Nadia Siala, Michela Tempia-Caliera, Jean-Pierre Hugot, Sabine Rakotobe, Christelle Lenoir, Anne Breton, Caterina Strisciuglio, Víctor Manuel Navas-López, Jan Melek, Alain Fischer, Frédéric Rieux-Laucat, Marie-Claude Stolzenberg, Eric Jeziorski, Yago González-Lama, Bénédicte Pigneur, Mongi Ben Hariz, Marina Aloi, Sylvain Latour, Fabienne Mazerolles, Christian Breuer, Julie Bruneau, Clara Crémilleux, Cecile Pelatan, Vaidotas Urbonas, Alexandre Fabre, Nadine Cerf-Bensussan, Frank M. Ruemmele, Luisa Mearin, Capucine Picard, Georgia Malamut, Neslihan Gurcan, Anders Paerregaard, Isabel Pinto Pais, Dan Turner, István Máttyus, Julie Rebeuh, Jiri Bronsky, Sylvain Hanein, Peter Lewindon, Rémi Duclaux-Loras, Graziella Guariso, Anne Bourrier, Odul Egritas Gurkan, Janos Major, Stéphanie Willot, Mara Cananzi, Marianna Parlato, Claudio Romano, Alain Lachaux, Matjaz Homan, Jorge Amil Dias, Eva Lévy, A Fischer, Stéphanie Coopman, Jan Krzysztof Nowak, Fernando Magro, Clémentine Dumant-Forest, Stephan Buderus, Bernadette Bègue, Fabienne Charbit-Henrion, Olivier Goulet, Evi Karanika, Alain Dabadie, Emmanuel Mas, Marta German Diaz, Cécile Fourrage, Rosa Lima, Charbit-Henrion, Fabienne, Parlato, Marianna, Hanein, Sylvain, Duclaux-Loras, Rémi, Nowak, Jan, Begue, Bernadette, Rakotobe, Sabine, Bruneau, Julie, Fourrage, Cécile, Alibeu, Olivier, Rieux-Laucat, Frédéric, Lévy, Eva, Stolzenberg, Marie-Claude, Mazerolles, Fabienne, Latour, Sylvain, Lenoir, Christelle, Fischer, Alain, Picard, Capucine, Aloi, Marina, Dias, Jorge Amil, Hariz, Mongi Ben, Bourrier, Anne, Breuer, Christian, Breton, Anne, Bronsky, Jiri, Buderus, Stephan, Cananzi, Mara, Coopman, Stéphanie, Crémilleux, Clara, Dabadie, Alain, Dumant-Forest, Clémentine, Gurkan, Odul Egrita, Fabre, Alexandre, Fischer, Aude, Diaz, Marta German, Gonzalez-Lama, Yago, Goulet, Olivier, Guariso, Graziella, Gurcan, Neslihan, Homan, Matjaz, Hugot, Jean-Pierre, Jeziorski, Eric, Karanika, Evi, Lachaux, Alain, Lewindon, Peter, Lima, Rosa, Magro, Fernando, Major, Jano, Malamut, Georgia, Mas, Emmanuel, Mattyus, Istvan, Mearin, Luisa M, Melek, Jan, Navas-Lopez, Victor Manuel, Paerregaard, Ander, Pelatan, Cecile, Pigneur, Bénédicte, Pais, Isabel Pinto, Rebeuh, Julie, Romano, Claudio, Siala, Nadia, Strisciuglio, Caterina, Tempia-Caliera, Michela, Tounian, Patrick, Turner, Dan, Urbonas, Vaidota, Willot, Stéphanie, Ruemmele, Frank M, and Cerf-Bensussan, Nadine
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VEO-IBD ,business.industry ,Yield (finance) ,monogenic IBD ,next generation sequencing ,very early onset IBD ,Gastroenterology ,Inflammatory Bowel Diseases ,Genetics and molecular epidemiology ,Original Articles ,General Medicine ,monogenic disorders ,Bioinformatics ,Very early onset ,DNA sequencing ,paediatrics ,Editor's Choice ,Multicenter study ,TNGS ,Medicine ,genetics and molecular epidemiology ,business - Abstract
Background and Aims An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.
- Published
- 2020
12. Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study.
- Author
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Charbit-Henrion F, Parlato M, Hanein S, Duclaux-Loras R, Nowak J, Begue B, Rakotobe S, Bruneau J, Fourrage C, Alibeu O, Rieux-Laucat F, Lévy E, Stolzenberg MC, Mazerolles F, Latour S, Lenoir C, Fischer A, Picard C, Aloi M, Dias JA, Hariz MB, Bourrier A, Breuer C, Breton A, Bronsky J, Buderus S, Cananzi M, Coopman S, Crémilleux C, Dabadie A, Dumant-Forest C, Gurkan OE, Fabre A, Fischer A, Diaz MG, Gonzalez-Lama Y, Goulet O, Guariso G, Gurcan N, Homan M, Hugot JP, Jeziorski E, Karanika E, Lachaux A, Lewindon P, Lima R, Magro F, Major J, Malamut G, Mas E, Mattyus I, Mearin LM, Melek J, Navas-Lopez VM, Paerregaard A, Pelatan C, Pigneur B, Pais IP, Rebeuh J, Romano C, Siala N, Strisciuglio C, Tempia-Caliera M, Tounian P, Turner D, Urbonas V, Willot S, Ruemmele FM, and Cerf-Bensussan N
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- 2021
- Full Text
- View/download PDF
13. Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study.
- Author
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Charbit-Henrion F, Parlato M, Hanein S, Duclaux-Loras R, Nowak J, Begue B, Rakotobe S, Bruneau J, Fourrage C, Alibeu O, Rieux-Laucat F, Lévy E, Stolzenberg MC, Mazerolles F, Latour S, Lenoir C, Fischer A, Picard C, Aloi M, Dias JA, Hariz MB, Bourrier A, Breuer C, Breton A, Bronsky J, Buderus S, Cananzi M, Coopman S, Crémilleux C, Dabadie A, Dumant-Forest C, Gurkan OE, Fabre A, Fischer A, Diaz MG, Gonzalez-Lama Y, Goulet O, Guariso G, Gurcan N, Homan M, Hugot JP, Jeziorski E, Karanika E, Lachaux A, Lewindon P, Lima R, Magro F, Major J, Malamut G, Mas E, Mattyus I, Mearin LM, Melek J, Navas-Lopez VM, Paerregaard A, Pelatan C, Pigneur B, Pais IP, Rebeuh J, Romano C, Siala N, Strisciuglio C, Tempia-Caliera M, Tounian P, Turner D, Urbonas V, Willot S, Ruemmele FM, and Cerf-Bensussan N
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- Adolescent, Age of Onset, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Inflammatory Bowel Diseases therapy, Male, Predictive Value of Tests, High-Throughput Nucleotide Sequencing, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases etiology
- Abstract
Background and Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment., Methods: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally., Results: Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES., Conclusions: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD., (© The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
- Published
- 2018
- Full Text
- View/download PDF
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