31 results on '"Keupp, Katharina"'
Search Results
2. Mutations in WNT1 Cause Different Forms of Bone Fragility
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Keupp, Katharina, Beleggia, Filippo, Kayserili, Hülya, Barnes, Aileen M., Steiner, Magdalena, Semler, Oliver, Fischer, Björn, Yigit, Gökhan, Janda, Claudia Y., Becker, Jutta, Breer, Stefan, Altunoglu, Umut, Grünhagen, Johannes, Krawitz, Peter, Hecht, Jochen, Schinke, Thorsten, Makareeva, Elena, Lausch, Ekkehart, Cankaya, Tufan, Caparrós-Martín, José A., Lapunzina, Pablo, Temtamy, Samia, Aglan, Mona, Zabel, Bernhard, Eysel, Peer, Koerber, Friederike, Leikin, Sergey, Garcia, K. Christopher, Netzer, Christian, Schönau, Eckhard, Ruiz-Perez, Victor L., Mundlos, Stefan, Amling, Michael, Kornak, Uwe, Marini, Joan, and Wollnik, Bernd
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- 2013
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3. RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome
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Bogershausen, Nina, Tsai, I-Chun, Pohl, Esther, Kiper, Pelin Ozlem Simsek, Beleggia, Filippo, Percin, E. Ferda, Keupp, Katharina, Matchan, Angela, Milz, Esther, Alanay, Yasemin, Kayserili, Hulya, Liu, Yicheng, Banka, Siddharth, Kranz, Andrea, Zenker, Martin, Wieczorek, Dagmar, Elcioglu, Nursel, Prontera, Paolo, Lyonnet, Stanislas, Meitinger, Thomas, Stewart, A. Francis, Donnai, Dian, Strom, Tim M., Boduroglu, Koray, Yigit, Gokhan, Li, Yun, Katsanis, Nicholas, and Wollnik, Bernd
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Physiological aspects ,Genetic aspects ,Research ,Risk factors ,Abnormalities ,Methyltransferases -- Abnormalities -- Physiological aspects -- Research ,Kabuki syndrome -- Risk factors -- Genetic aspects -- Research ,Methyltransferases - Abstract
Introduction De novo dominant germline mutations in lysine (K)-specific methyltransferase 2D (KMT2D; formerly MLL2, ALR; ref. 1) or lysine (K)-specific demethylase 6A (KDM6A) cause Kabuki syndrome (KS; MIM 147920 and [...], The genetic disorder Kabuki syndrome (KS) is characterized by developmental delay and congenital anomalies. Dominant mutations in the chromatin regulators lysine (K)-specific methyltransferase 2D (KMT2D) (also known as MLL2) and lysine (K)-specific demethylase 6A (KDM6A) underlie the majority of cases. Although the functions of these chromatin-modifying proteins have been studied extensively, the physiological systems regulated by them are largely unknown. Using whole-exome sequencing, we identified a mutation in RAP1A that was converted to homozygosity as the result of uniparental isodisomy (UPD) in a patient with KS and a de novo, dominant mutation in RAP1B in a second individual with a KS-like phenotype. We elucidated a genetic and functional interaction between the respective KS-associated genes and their products in zebrafish models and patient cell lines. Specifically, we determined that dysfunction of known KS genes and the genes identified in this study results in aberrant MEK/ERK signaling as well as disruption of F-actin polymerization and cell intercalation. Moreover, these phenotypes could be rescued in zebrafish models by rebalancing MEK/ERK signaling via administration of small molecule inhibitors of MEK. Taken together, our studies suggest that the KS pathophysiology overlaps with the RASopathies and provide a potential direction for treatment design.
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- 2015
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4. Attenuated BMP1 Function Compromises Osteogenesis, Leading to Bone Fragility in Humans and Zebrafish
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Asharani, P.V., Keupp, Katharina, Semler, Oliver, Wang, Wenshen, Li, Yun, Thiele, Holger, Yigit, Gökhan, Pohl, Esther, Becker, Jutta, Frommolt, Peter, Sonntag, Carmen, Altmüller, Janine, Zimmermann, Katharina, Greenspan, Daniel S., Akarsu, Nurten A., Netzer, Christian, Schönau, Eckhard, Wirth, Radu, Hammerschmidt, Matthias, Nürnberg, Peter, Wollnik, Bernd, and Carney, Thomas J.
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- 2012
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5. The missing “link”: an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation
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Schreml, Julia, Durmaz, Burak, Cogulu, Ozgur, Keupp, Katharina, Beleggia, Filippo, Pohl, Esther, Milz, Esther, Coker, Mahmut, Ucar, Sema Kalkan, Nürnberg, Gudrun, Nürnberg, Peter, Kuhn, Joachim, and Ozkinay, Ferda
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- 2014
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6. A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome
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Pohl, Esther, Aykut, Ayca, Beleggia, Filippo, Karaca, Emin, Durmaz, Burak, Keupp, Katharina, Arslan, Esra, Onay, Melis Palamar, Yigit, Gökhan, Özkinay, Ferda, and Wollnik, Bernd
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- 2013
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7. HerediCaRe: Dokumentations- und IT-Lösung eines spezialisierten Registers für erblichen Brust- und Eierstockkrebs
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Engel, Christoph, primary, Wieland, Kerstin, primary, Zachariae, Silke, additional, Bucksch, Karolin, additional, Enders, Ute, additional, Schoenwiese, Ulrike, additional, Yahiaoui-Doktor, Maryam, additional, Keupp, Katharina, additional, Waha, Anke, additional, Hahnen, Eric, additional, Remy, Robert, additional, Ernst, Corinna, additional, Loeffler, Markus, additional, and Schmutzler, Rita K., additional
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- 2021
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8. A mutation screen in patients with Kabuki syndrome
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Li, Yun, Bögershausen, Nina, Alanay, Yasemin, Simsek Kiper, Pelin Özlem, Plume, Nadine, Keupp, Katharina, Pohl, Esther, Pawlik, Barbara, Rachwalski, Martin, Milz, Esther, Thoenes, Michaela, Albrecht, Beate, Prott, Eva-Christina, Lehmkühler, Margret, Demuth, Stephanie, Utine, Gülen Eda, Boduroglu, Koray, Frankenbusch, Katja, Borck, Guntram, Gillessen-Kaesbach, Gabriele, Yigit, Gökhan, Wieczorek, Dagmar, and Wollnik, Bernd
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- 2011
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9. HerediCaRe: Documentation and IT Solution of a Specialized Registry for Hereditary Breast and Ovarian Cancer
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Engel, Christoph, Wieland, Kerstin, Zachariae, Silke, Bucksch, Karolin, Enders, Ute, Schoenwiese, Ulrike, Yahiaoui-Doktor, Maryam, Keupp, Katharina, Waha, Anke, Hahnen, Eric, Remy, Robert, Ernst, Corinna, Loeffler, Markus, Schmutzler, Rita K., Engel, Christoph, Wieland, Kerstin, Zachariae, Silke, Bucksch, Karolin, Enders, Ute, Schoenwiese, Ulrike, Yahiaoui-Doktor, Maryam, Keupp, Katharina, Waha, Anke, Hahnen, Eric, Remy, Robert, Ernst, Corinna, Loeffler, Markus, and Schmutzler, Rita K.
- Abstract
Zusammenfassung Das nationale Register HerediCaRe fur die Evaluation und Verbesserung der risiko-adjustierten Pravention bei erblichem Brust- und Eierstockkrebs ist eines von sechs vom BMBF geforderten modellhaften Registern in der Versorgungsforschung. In diesem Beitrag beschreiben und diskutieren wir die zur standardisierten Datenerfassung gewahlte Dokumentations- und IT-Losung auf der Basis der zuvor definierten speziellen funktionalen Anforderungen. Die Dokumentation gliedert sich in verschiedene patientenindividuell einzusetzende Module, die auf einem zuvor festgelegten Merkmalskatalog beruhen. Aufgrund spezieller funktionaler Anforderungen wurde eine eigene Datenerfassungsanwendung auf der Basis von ORACLE und ORACLE Forms entwickelt und implementiert. Die speziellen Anforderungen umfassten u.a. die Einbindung grafischer Stammbaumdarstellungen, den strukturierten Upload von Stammbaumdaten und molekulargenetischen Informationen, die automatisierte Altdatenubernahme aus dem Vorgangersystem, sowie die freie Programmierbarkeit von beliebig komplexen Datenbankabfragen zur zentralen Datenqualitatsprufung. In die Anwendung ist eine Datenbank zur patienten-unabhangigen Verwaltung genetischer Risikovarianten nahtlos integriert und mit den patientenbezogenen Daten verknupft. Die Vor- und Nachteile der gewahlten IT-Losung werden kritisch diskutiert. Insgesamt kommen wir zu der Schlussfolgerung, dass es angesichts der komplexen Dokumentation und der speziellen Funktionsanforderungen alternativ keine fertigen Softwareprodukte zu der von uns gewahlten Eigenentwicklung existieren. Abstract The national registry HerediCaRe for the evaluation and improvement of risk-adjusted prevention in hereditary breast and ovarian cancer is one of six model registries in health services research funded by the BMBF. In this paper, we describe and discuss the documentation and IT solution chosen for standardized data collection based on the specific functional requirements previously defined
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- 2021
10. Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta
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Moosa, Shahida, Yamamoto, Guilherme L., Garbes, Lutz, Keupp, Katharina, Beleza-Meireles, Ana, Moreno, Carolina Araujo, Valadares, Eugenia Ribeiro, de Sousa, Sérgio B., Maia, Sofia, Saraiva, Jorge, Honjo, Rachel S., Kim, Chong Ae, Cabral de Menezes, Hamilton, Lausch, Ekkehart, Lorini, Pablo Villavicencio, Lamounier, Arsonval, Jr., Carniero, Tulio Canella Bezerra, Giunta, Cecilia, Rohrbach, Marianne, Janner, Marco, Semler, Oliver, Beleggia, Filippo, Li, Yun, Yigit, Gökhan, Reintjes, Nadine, Altmüller, Janine, Nürnberg, Peter, Cavalcanti, Denise P., Zabel, Bernhard, Warman, Matthew L., Bertola, Debora R., Wollnik, Bernd, and Netzer, Christian
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- 2019
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11. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
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Parsons, Michael T., primary, Tudini, Emma, additional, Li, Hongyan, additional, Hahnen, Eric, additional, Wappenschmidt, Barbara, additional, Feliubadaló, Lidia, additional, Aalfs, Cora M., additional, Agata, Simona, additional, Aittomäki, Kristiina, additional, Alducci, Elisa, additional, Alonso‐Cerezo, María Concepción, additional, Arnold, Norbert, additional, Auber, Bernd, additional, Austin, Rachel, additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barbieri, Elena, additional, Bartram, Claus R., additional, Blanco, Ana, additional, Blümcke, Britta, additional, Bonache, Sandra, additional, Bonanni, Bernardo, additional, Borg, Åke, additional, Bortesi, Beatrice, additional, Brunet, Joan, additional, Bruzzone, Carla, additional, Bucksch, Karolin, additional, Cagnoli, Giulia, additional, Caldés, Trinidad, additional, Caliebe, Almuth, additional, Caligo, Maria A., additional, Calvello, Mariarosaria, additional, Capone, Gabriele L., additional, Caputo, Sandrine M., additional, Carnevali, Ileana, additional, Carrasco, Estela, additional, Caux‐Moncoutier, Virginie, additional, Cavalli, Pietro, additional, Cini, Giulia, additional, Clarke, Edward M., additional, Concolino, Paola, additional, Cops, Elisa J., additional, Cortesi, Laura, additional, Couch, Fergus J., additional, Darder, Esther, additional, Hoya, Miguel, additional, Dean, Michael, additional, Debatin, Irmgard, additional, Del Valle, Jesús, additional, Delnatte, Capucine, additional, Derive, Nicolas, additional, Diez, Orland, additional, Ditsch, Nina, additional, Domchek, Susan M., additional, Dutrannoy, Véronique, additional, Eccles, Diana M., additional, Ehrencrona, Hans, additional, Enders, Ute, additional, Evans, D. Gareth, additional, Farra, Chantal, additional, Faust, Ulrike, additional, Felbor, Ute, additional, Feroce, Irene, additional, Fine, Miriam, additional, Foulkes, William D., additional, Galvao, Henrique C.R., additional, Gambino, Gaetana, additional, Gehrig, Andrea, additional, Gensini, Francesca, additional, Gerdes, Anne‐Marie, additional, Germani, Aldo, additional, Giesecke, Jutta, additional, Gismondi, Viviana, additional, Gómez, Carolina, additional, Garcia, Encarna B., additional, González, Sara, additional, Grau, Elia, additional, Grill, Sabine, additional, Gross, Eva, additional, Guerrieri‐Gonzaga, Aliana, additional, Guillaud‐Bataille, Marine, additional, Gutiérrez‐Enríquez, Sara, additional, Haaf, Thomas, additional, Hackmann, Karl, additional, Hansen, Thomas V.O., additional, Harris, Marion, additional, Hauke, Jan, additional, Heinrich, Tilman, additional, Hellebrand, Heide, additional, Herold, Karen N., additional, Honisch, Ellen, additional, Horvath, Judit, additional, Houdayer, Claude, additional, Hübbel, Verena, additional, Iglesias, Silvia, additional, Izquierdo, Angel, additional, James, Paul A., additional, Janssen, Linda A.M., additional, Jeschke, Udo, additional, Kaulfuß, Silke, additional, Keupp, Katharina, additional, Kiechle, Marion, additional, Kölbl, Alexandra, additional, Krieger, Sophie, additional, Kruse, Torben A., additional, Kvist, Anders, additional, Lalloo, Fiona, additional, Larsen, Mirjam, additional, Lattimore, Vanessa L., additional, Lautrup, Charlotte, additional, Ledig, Susanne, additional, Leinert, Elena, additional, Lewis, Alexandra L., additional, Lim, Joanna, additional, Loeffler, Markus, additional, López‐Fernández, Adrià, additional, Lucci‐Cordisco, Emanuela, additional, Maass, Nicolai, additional, Manoukian, Siranoush, additional, Marabelli, Monica, additional, Matricardi, Laura, additional, Meindl, Alfons, additional, Michelli, Rodrigo D., additional, Moghadasi, Setareh, additional, Moles‐Fernández, Alejandro, additional, Montagna, Marco, additional, Montalban, Gemma, additional, Monteiro, Alvaro N., additional, Montes, Eva, additional, Mori, Luigi, additional, Moserle, Lidia, additional, Müller, Clemens R., additional, Mundhenke, Christoph, additional, Naldi, Nadia, additional, Nathanson, Katherine L., additional, Navarro, Matilde, additional, Nevanlinna, Heli, additional, Nichols, Cassandra B., additional, Niederacher, Dieter, additional, Nielsen, Henriette R., additional, Ong, Kai‐ren, additional, Pachter, Nicholas, additional, Palmero, Edenir I., additional, Papi, Laura, additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Perez‐Segura, Pedro, additional, Pfeifer, Katharina, additional, Pineda, Marta, additional, Pohl‐Rescigno, Esther, additional, Poplawski, Nicola K., additional, Porfirio, Berardino, additional, Quante, Anne S., additional, Ramser, Juliane, additional, Reis, Rui M., additional, Revillion, Françoise, additional, Rhiem, Kerstin, additional, Riboli, Barbara, additional, Ritter, Julia, additional, Rivera, Daniela, additional, Rofes, Paula, additional, Rump, Andreas, additional, Salinas, Monica, additional, Sánchez de Abajo, Ana María, additional, Schmidt, Gunnar, additional, Schoenwiese, Ulrike, additional, Seggewiß, Jochen, additional, Solanes, Ares, additional, Steinemann, Doris, additional, Stiller, Mathias, additional, Stoppa‐Lyonnet, Dominique, additional, Sullivan, Kelly J., additional, Susman, Rachel, additional, Sutter, Christian, additional, Tavtigian, Sean V., additional, Teo, Soo H., additional, Teulé, Alex, additional, Thomassen, Mads, additional, Tibiletti, Maria Grazia, additional, Tischkowitz, Marc, additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Tornero, Eva, additional, Törngren, Therese, additional, Torres‐Esquius, Sara, additional, Toss, Angela, additional, Trainer, Alison H., additional, Tucker, Katherine M., additional, Asperen, Christi J., additional, Mackelenbergh, Marion T., additional, Varesco, Liliana, additional, Vargas‐Parra, Gardenia, additional, Varon, Raymonda, additional, Vega, Ana, additional, Velasco, Ángela, additional, Vesper, Anne‐Sophie, additional, Viel, Alessandra, additional, Vreeswijk, Maaike P. G., additional, Wagner, Sebastian A., additional, Waha, Anke, additional, Walker, Logan C., additional, Walters, Rhiannon J., additional, Wang‐Gohrke, Shan, additional, Weber, Bernhard H. F., additional, Weichert, Wilko, additional, Wieland, Kerstin, additional, Wiesmüller, Lisa, additional, Witzel, Isabell, additional, Wöckel, Achim, additional, Woodward, Emma R., additional, Zachariae, Silke, additional, Zampiga, Valentina, additional, Zeder‐Göß, Christine, additional, Investigators, KConFab, additional, Lázaro, Conxi, additional, Nicolo, Arcangela, additional, Radice, Paolo, additional, Engel, Christoph, additional, Schmutzler, Rita K., additional, Goldgar, David E., additional, and Spurdle, Amanda B., additional
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- 2019
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12. Biallelic germline BRCA1 mutations in a patient with early onset breast cancer, mild Fanconi anemia‐like phenotype, and no chromosome fragility
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Keupp, Katharina, primary, Hampp, Stephanie, additional, Hübbel, Annette, additional, Maringa, Monika, additional, Kostezka, Sarah, additional, Rhiem, Kerstin, additional, Waha, Anke, additional, Wappenschmidt, Barbara, additional, Pujol, Roser, additional, Surrallés, Jordi, additional, Schmutzler, Rita K., additional, Wiesmüller, Lisa, additional, and Hahnen, Eric, additional
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- 2019
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13. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
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Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., Spurdle, Amanda B., Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., and Spurdle, Amanda B.
- Abstract
The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.
- Published
- 2019
14. Biallelic germline BRCA1 mutations in a patient with early onset breast cancer, mild Fanconi anemia-like phenotype, and no chromosome fragility
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Keupp, Katharina, Hampp, Stephanie, Huebbel, Annette, Maringa, Monika, Kostezka, Sarah, Rhiem, Kerstin, Waha, Anke, Wappenschmidt, Barbara, Pujol, Roser, Surralles, Jordi, Schmutzler, Rita K., Wiesmueller, Lisa, Hahnen, Eric, Keupp, Katharina, Hampp, Stephanie, Huebbel, Annette, Maringa, Monika, Kostezka, Sarah, Rhiem, Kerstin, Waha, Anke, Wappenschmidt, Barbara, Pujol, Roser, Surralles, Jordi, Schmutzler, Rita K., Wiesmueller, Lisa, and Hahnen, Eric
- Abstract
Background Biallelic BRCA1 mutations are regarded either embryonically lethal or to cause Fanconi anemia (FA), a genomic instability syndrome characterized by bone marrow failure, developmental abnormalities, and cancer predisposition. We report biallelic BRCA1 mutations c.181T > G (p.Cys61Gly) and c.5096G > A (p.Arg1699Gln) in a woman with breast cancer diagnosed at the age of 30 years. The common European founder mutation p.Cys61Gly confers high cancer risk, whereas the deleterious p.Arg1699Gln is hypomorphic and was suggested to confer intermediate cancer risk. Methods and Results Aside from significant toxicity from chemotherapy, the patient showed mild FA-like features (e.g., short stature, microcephaly, skin hyperpigmentation). Chromosome fragility, a hallmark of FA patient cells, was not present in patient-derived peripheral blood lymphocytes. We demonstrated that the p.Arg1699Gln mutation impairs DNA double-strand break repair, elevates RAD51 foci levels at baseline, and compromises BRCA1 protein function in protecting from replication stress. Although the p.Arg1699Gln mutation compromises BRCA1 function, the residual activity of the p.Arg1699Gln allele likely prevents from chromosome fragility and a more severe FA phenotype. Conclusion Our data expand the clinical spectrum associated with biallelic BRCA1 mutations, ranging from embryonic lethality to a mild FA-like phenotype and no chromosome fragility.
- Published
- 2019
15. Erratum to: A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome
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Pohl, Esther, Aykut, Ayca, Beleggia, Filippo, Karaca, Emin, Durmaz, Burak, Keupp, Katharina, Arslan, Esra, Palamar, Melis, Yigit, Gökhan, Özkinay, Ferda, and Wollnik, Bernd
- Published
- 2013
- Full Text
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16. Non-small cell neuroendocrine carcinoma of the ovary in a BRCA2-germline mutation carrier: A case report and brief review of the literature
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Herold, Natalie, Wappenschmidt, Barbara, Markiefka, Birgid, Keupp, Katharina, Kroeber, Sandra, Hahnen, Eric, Schmutzler, Rita, Rhiem, Kerstin, Herold, Natalie, Wappenschmidt, Barbara, Markiefka, Birgid, Keupp, Katharina, Kroeber, Sandra, Hahnen, Eric, Schmutzler, Rita, and Rhiem, Kerstin
- Abstract
Non-small cell neuroendocrine carcinomas (NSCNEC) account for 2% of gynecological cancer cases and are associated with a poor prognosis due to delayed diagnosis and aggressive tumor behavior. BRCA2-associated ovarian carcinomas predominantly possess a high-grade serous phenotype, which respond to platinum and targeted therapy with PARP inhibitors. Presented here is the case of an adult patient with NSCNEC of the ovaries associated with a deleterious BRCA2 germline mutation. The pathogenic mutation was also confirmed on the somatic level, while the wild-type allele had a high variant fraction, suggesting loss of heterozygosity. To the best of our knowledge, this is the first report of an adult BRCA2 germline mutation carrier with the rare NSCNEC of the ovary phenotype. Therefore, ovarian cancer patients with histological subtypes other than high-grade serous carcinomas should be tested for BRCA1/2 mutations, as they may benefit from targeted therapy with poly (ADP-ribose) polymerase inhibitors.
- Published
- 2018
17. Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer
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Hauke, Jan, Horvath, Judit, Gross, Eva, Gehrig, Andrea, Honisch, Ellen, Hackmann, Karl, Schmidt, Gunnar, Arnold, Norbert, Faust, Ulrike, Sutter, Christian, Hentschel, Julia, Wang-Gohrke, Shan, Smogavec, Mateja, Weber, Bernhard H. F., Weber-Lassalle, Nana, Weber-Lassalle, Konstantin, Borde, Julika, Ernst, Corinna, Altmueller, Janine, Volk, Alexander E., Thiele, Holger, Huebbel, Verena, Nuernberg, Peter, Keupp, Katharina, Versmold, Beatrix, Pohl, Esther, Kubisch, Christian, Grill, Sabine, Paul, Victoria, Herold, Natalie, Lichey, Nadine, Rhiem, Kerstin, Ditsch, Nina, Ruckert, Christian, Wappenschmidt, Barbara, Auber, Bernd, Rump, Andreas, Niederacher, Dieter, Haaf, Thomas, Ramser, Juliane, Dworniczak, Bernd, Engel, Christoph, Meindl, Alfons, Schmutzler, Rita K., Hahnen, Eric, Hauke, Jan, Horvath, Judit, Gross, Eva, Gehrig, Andrea, Honisch, Ellen, Hackmann, Karl, Schmidt, Gunnar, Arnold, Norbert, Faust, Ulrike, Sutter, Christian, Hentschel, Julia, Wang-Gohrke, Shan, Smogavec, Mateja, Weber, Bernhard H. F., Weber-Lassalle, Nana, Weber-Lassalle, Konstantin, Borde, Julika, Ernst, Corinna, Altmueller, Janine, Volk, Alexander E., Thiele, Holger, Huebbel, Verena, Nuernberg, Peter, Keupp, Katharina, Versmold, Beatrix, Pohl, Esther, Kubisch, Christian, Grill, Sabine, Paul, Victoria, Herold, Natalie, Lichey, Nadine, Rhiem, Kerstin, Ditsch, Nina, Ruckert, Christian, Wappenschmidt, Barbara, Auber, Bernd, Rump, Andreas, Niederacher, Dieter, Haaf, Thomas, Ramser, Juliane, Dworniczak, Bernd, Engel, Christoph, Meindl, Alfons, Schmutzler, Rita K., and Hahnen, Eric
- Abstract
The prevalence of germ line mutations in non-BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK2 gene (2.5%), followed by ATM (1.5%) and PALB2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM (OR: 3.63, 95% CI: 2.67-4.94), CDH1 (OR: 17.04, 95% CI: 3.54-82), CHEK2 (OR: 2.93, 95% CI: 2.29-3.75), PALB2 (OR: 9.53, 95% CI: 6.25-14.51), and TP53 (OR: 7.30, 95% CI: 1.22-43.68). NBN germ line mutations were not significantly associated with BC risk (OR: 1.39, 95% CI: 0.73-2.64). Due to their low mutation prevalence, the RAD51C and RAD51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK2 and TP53 in BC index patients. Compared with the overall sample, only TP53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK2, PALB2, and TP53 genes with bilateral BC. Both, ATM and CHEK2, were negatively associated with triple-negative breast cancer (TNBC) and estrogen receptor (ER)-negative tumor phenotypes. A particularly high CHEK2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors.
- Published
- 2018
18. Gene panel testing of 5589 BRCA1/2 -negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer
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Hauke, Jan, primary, Horvath, Judit, additional, Groß, Eva, additional, Gehrig, Andrea, additional, Honisch, Ellen, additional, Hackmann, Karl, additional, Schmidt, Gunnar, additional, Arnold, Norbert, additional, Faust, Ulrike, additional, Sutter, Christian, additional, Hentschel, Julia, additional, Wang-Gohrke, Shan, additional, Smogavec, Mateja, additional, Weber, Bernhard H. F., additional, Weber-Lassalle, Nana, additional, Weber-Lassalle, Konstantin, additional, Borde, Julika, additional, Ernst, Corinna, additional, Altmüller, Janine, additional, Volk, Alexander E., additional, Thiele, Holger, additional, Hübbel, Verena, additional, Nürnberg, Peter, additional, Keupp, Katharina, additional, Versmold, Beatrix, additional, Pohl, Esther, additional, Kubisch, Christian, additional, Grill, Sabine, additional, Paul, Victoria, additional, Herold, Natalie, additional, Lichey, Nadine, additional, Rhiem, Kerstin, additional, Ditsch, Nina, additional, Ruckert, Christian, additional, Wappenschmidt, Barbara, additional, Auber, Bernd, additional, Rump, Andreas, additional, Niederacher, Dieter, additional, Haaf, Thomas, additional, Ramser, Juliane, additional, Dworniczak, Bernd, additional, Engel, Christoph, additional, Meindl, Alfons, additional, Schmutzler, Rita K., additional, and Hahnen, Eric, additional
- Published
- 2018
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19. Non-small cell neuroendocrine carcinoma of the ovary in a BRCA2-germline mutation carrier: A case report and brief review of the literature
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Herold, Natalie, primary, Wappenschmidt, Barbara, additional, Markiefka, Birgid, additional, Keupp, Katharina, additional, Kr�ber, Sandra, additional, Hahnen, Eric, additional, Schmutzler, Rita, additional, and Rhiem, Kerstin, additional
- Published
- 2018
- Full Text
- View/download PDF
20. Spotlight on the pathogenesis of Kabuki syndrome
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Bögershausen, Nina, ŞİMŞEK KİPER, PELİN ÖZLEM, Keupp, Katharina, Yiğit, Gökhan, BODUROĞLU, OSMAN KORAY, Strom, Tim M, Donnai, Dian, Stewart, Francis, Meitinger, Thomas, Lyonnet, Stanislas, Prontera, Paolo, ELÇİOĞLU, HURİYE NURSEL, Wieczorek, Dagmar, Zenker, Martin, Kranz, Andrea, Banka, Siddharth, Liu, Yicheng, KAYSERİLİ KARABEY, HÜLYA, ALANAY, YASEMİN, Angela, Matchan, Wollnik, Bernd, Beleggia, Filippo, Pohl, Esther, Tsai, I Chun, PERÇİN, FERDA EMRİYE, Li, Yun, and Katsanis, Nicholas
- Published
- 2015
21. Rap1-Mediated Mek/Erk Pathway Defects In Kabuki Syndrome
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Boegershausen, Nina, Tsai, I-Chun, Pohl, Esther, Kiper, Pelin Ozlem Simsek, Beleggia, Filippo, Percin, E. Ferda, Keupp, Katharina, Matchan, Angela, Milz, Esther, Alanay, Yasemin, Kayserili, Hulya, Liu, Yicheng, Banka, Siddharth, Kranz, Andrea, Zenker, Martin, Wieczorek, Dagmar, Elcioglu, Nursel, Prontera, Paolo, Lyonnet, Stanislas, and Meitinger, Thomas
- Abstract
The genetic disorder Kabuki syndrome (KS) is characterized by developmental delay and congenital anomalies. Dominant mutations in the chromatin regulators lysine (K)-specific methyltransferase 2D (KMT2D) (also known as MLL2) and lysine (K)-specific demethylase 6A (KDM6A) underlie the majority of cases. Although the functions of these chromatin-modifying proteins have been studied extensively, the physiological systems regulated by them are largely unknown. Using whole-exome sequencing, we identified a mutation in RAP1A that was converted to homozygosity as the result of uniparental isodisomy (UPD) in a patient with KS and a de novo, dominant mutation in RAP1B in a second individual with a KS-like phenotype. We elucidated a genetic and functional interaction between the respective KS-associated genes and their products in zebrafish models and patient cell lines. Specifically, we determined that dysfunction of known KS genes and the genes identified in this study results in aberrant MEK/ERK signaling as well as disruption of F-actin polymerization and cell intercalation. Moreover, these phenotypes could be rescued in zebrafish models by rebalancing MEK/ERK signaling via administration of small molecule inhibitors of MEK. Taken together, our studies suggest that the KS pathophysiology overlaps with the RASopathies and provide a potential direction for treatment design.
- Published
- 2015
22. Recessive TRAPPC11 Mutations Cause a Disease Spectrum of Limb Girdle Muscular Dystrophy and Myopathy with Movement Disorder and Intellectual Disability
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Bögershausen, Nina, Shahrzad, Nassim, Chong, Jessica X., von Kleist-Retzow, Jürgen-Christoph, Stanga, Daniela, Li, Yun, Bernier, Francois P., Loucks, Catrina M., Wirth, Radu, Puffenberger, Eric G., Hegele, Robert A., Schreml, Julia, Lapointe, Gabriel, Keupp, Katharina, Brett, Christopher L., Anderson, Rebecca, Hahn, Andreas, Innes, A. Micheil, Suchowersky, Oksana, Mets, Marilyn B., Nürnberg, Gudrun, McLeod, D. Ross, Thiele, Holger, Waggoner, Darrel, Altmüller, Janine, Boycott, Kym M., Schoser, Benedikt, Nürnberg, Peter, Ober, Carole, Heller, Raoul, Parboosingh, Jillian S., Wollnik, Bernd, Sacher, Michael, and Lamont, Ryan E.
- Published
- 2013
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23. Novel insights into molecular mechanisms of inherited bone disorders
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Keupp, Katharina
- Subjects
ddc:500 ,ddc:610 - Published
- 2013
24. A Mutation in the 5′-UTR of IFITM5 Creates an In-Frame Start Codon and Causes Autosomal-Dominant Osteogenesis Imperfecta Type V with Hyperplastic Callus
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Semler, Oliver, Garbes, Lutz, Keupp, Katharina, Swan, Daniel, Zimmermann, Katharina, Becker, Jutta, Iden, Sandra, Wirth, Brunhilde, Eysel, Peer, Koerber, Friederike, Schoenau, Eckhard, Bohlander, Stefan K., Wollnik, Bernd, and Netzer, Christian
- Published
- 2012
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25. RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome
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Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), Boegershausen, Nina; Tsai, I-Chu; Pohl, Esther; Kiper, Pelin Özlem Şimşek; Beleggia, Filippo; Percin, E. Ferda; Keupp, Katharina; Matchan, Angela; Milz, Esther; Alanay, Yasemin; Liu, Yicheng; Banka, Siddharth; Kranz, Andrea; Zenker, Martin; Wieczorek, Dagmar; Elçioğlu, Nursel; Prontera, Paolo; Lyonnet, Stanislas; Meitinger, Thomas; Stewart, A. Francis; Donnai, Dian; Strom, Tim M.; Boduroğlu, Koray; Yiğit, Gökhan; Li, Yun; Katsanis, Nicholas; Wollnik, Bernd, School of Medicine, Department of Medical Genetics, Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), Boegershausen, Nina; Tsai, I-Chu; Pohl, Esther; Kiper, Pelin Özlem Şimşek; Beleggia, Filippo; Percin, E. Ferda; Keupp, Katharina; Matchan, Angela; Milz, Esther; Alanay, Yasemin; Liu, Yicheng; Banka, Siddharth; Kranz, Andrea; Zenker, Martin; Wieczorek, Dagmar; Elçioğlu, Nursel; Prontera, Paolo; Lyonnet, Stanislas; Meitinger, Thomas; Stewart, A. Francis; Donnai, Dian; Strom, Tim M.; Boduroğlu, Koray; Yiğit, Gökhan; Li, Yun; Katsanis, Nicholas; Wollnik, Bernd, School of Medicine, and Department of Medical Genetics
- Abstract
The genetic disorder Kabuki syndrome (KS) is characterized by developmental delay and congenital anomalies. Dominant mutations in the chromatin regulators lysine (K)-specific methyltransferase 2D (KMT2D) (also known as MLL2) and lysine (K)-specific demethylase 6A (KDM6A) underlie the majority of cases. Although the functions of these chromatin-modifying proteins have been studied extensively, the physiological systems regulated by them are largely unknown. Using whole-exome sequencing, we identified a mutation in RAP1A that was converted to homozygosity as the result of uniparental isodisomy (UPD) in a patient with KS and a de novo, dominant mutation in RAP1B in a second individual with a KS-like phenotype. We elucidated a genetic and functional interaction between the respective KS-associated genes and their products in zebrafish models and patient cell lines. Specifically, we determined that dysfunction of known KS genes and the genes identified in this study results in aberrant MEK/ERK signaling as well as disruption of F-actin polymerization and cell intercalation. Moreover, these phenotypes could be rescued in zebrafish models by rebalancing MEK/ERK signaling via administration of small molecule inhibitors of MEK. Taken together, our studies suggest that the KS pathophysiology overlaps with the RASopathies and provide a potential direction for treatment design., German Federal Ministry of Education and Research (BMBF); E-RARE network CRANIRARE-2; national rare disease network FACE; Scientific and Technological Research Council of Turkey (TÜBİTAK); NIH; NRSA; Else Kroner-Fresenius-Stiftung
- Published
- 2015
26. Mutations in the interleukin receptor cause autosomal recessive Crouzon-like craniosynostosis
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Keupp, Katharina, Li, Yun, Vargel, Ibrahim, Hoischen, Alexander, Richardson, Rebecca, Neveling, Kornelia, Alanay, Yasemin, Uz, Elif, Elcioğlu, Nursel, Rachwalski, Martin, Kamaci, Soner, Tunçbilek, Gökhan, Akin, Burcu, Grötzinger, Joachim, Konas, Ersoy, Mavili, Emin, Müller-Newen, Gerhard, Collmann, Hartmut, Roscioli, Tony ; https://orcid.org/0000-0003-1502-5000, Buckley, Michael F, Yigit, Gökhan, Gilissen, Christian, Kress, Wolfram, Veltman, Joris, Hammerschmidt, Matthias, Akarsu, Nurten A, Wollnik, Bernd, Keupp, Katharina, Li, Yun, Vargel, Ibrahim, Hoischen, Alexander, Richardson, Rebecca, Neveling, Kornelia, Alanay, Yasemin, Uz, Elif, Elcioğlu, Nursel, Rachwalski, Martin, Kamaci, Soner, Tunçbilek, Gökhan, Akin, Burcu, Grötzinger, Joachim, Konas, Ersoy, Mavili, Emin, Müller-Newen, Gerhard, Collmann, Hartmut, Roscioli, Tony ; https://orcid.org/0000-0003-1502-5000, Buckley, Michael F, Yigit, Gökhan, Gilissen, Christian, Kress, Wolfram, Veltman, Joris, Hammerschmidt, Matthias, Akarsu, Nurten A, and Wollnik, Bernd
- Abstract
We have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis.
- Published
- 2013
27. A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome (vol 132, pg 1311, 2013)
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Pohl, Esther, Aykut, Ayca, Beleggia, Filippo, Karaca, Emin, Durmaz, Burak, Keupp, Katharina, Arslan, Esra, Palamar, Melis, Yigit, Goekhan, Ozkinay, Ferda, Wollnik, Bernd, Pohl, Esther, Aykut, Ayca, Beleggia, Filippo, Karaca, Emin, Durmaz, Burak, Keupp, Katharina, Arslan, Esra, Palamar, Melis, Yigit, Goekhan, Ozkinay, Ferda, and Wollnik, Bernd
- Published
- 2013
28. The missing “link”: an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation
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Schreml, Julia, primary, Durmaz, Burak, additional, Cogulu, Ozgur, additional, Keupp, Katharina, additional, Beleggia, Filippo, additional, Pohl, Esther, additional, Milz, Esther, additional, Coker, Mahmut, additional, Ucar, Sema Kalkan, additional, Nürnberg, Gudrun, additional, Nürnberg, Peter, additional, Kuhn, Joachim, additional, and Ozkinay, Ferda, additional
- Published
- 2013
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29. Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon‐like craniosynostosis
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Keupp, Katharina, primary, Li, Yun, additional, Vargel, Ibrahim, additional, Hoischen, Alexander, additional, Richardson, Rebecca, additional, Neveling, Kornelia, additional, Alanay, Yasemin, additional, Uz, Elif, additional, Elcioğlu, Nursel, additional, Rachwalski, Martin, additional, Kamaci, Soner, additional, Tunçbilek, Gökhan, additional, Akin, Burcu, additional, Grötzinger, Joachim, additional, Konas, Ersoy, additional, Mavili, Emin, additional, Müller‐Newen, Gerhard, additional, Collmann, Hartmut, additional, Roscioli, Tony, additional, Buckley, Michael F., additional, Yigit, Gökhan, additional, Gilissen, Christian, additional, Kress, Wolfram, additional, Veltman, Joris, additional, Hammerschmidt, Matthias, additional, Akarsu, Nurten A., additional, and Wollnik, Bernd, additional
- Published
- 2013
- Full Text
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30. Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis
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Keupp, Katharina, Li, Yun, Vargel, Ibrahim, Hoischen, Alexander, Richardson, Rebecca, Neveling, Kornelia, Alanay, Yasemin, Uz, Elif, Elcioglu, Nursel, Rachwalski, Martin, Kamaci, Soner, Tunçbilek, Gökhan, Akin, Burcu, Grötzinger, Joachim, Konas, Ersoy, Mavili, Emin, Müller-Newen, Gerhard, Collmann, Hartmut, Roscioli, Tony, Buckley, Michael F., Yigit, Gökhan, Gilissen, Christian, Kress, Wolfram, Veltman, Joris A., Hammerschmidt, Matthias, Akarsu, Nurten A., and Wollnik, Bernd
- Subjects
3. Good health - Abstract
Molecular genetics & genomic medicine : MGGM 1(4), 223-237 (2013). doi:10.1002/mgg3.28, Published by Wiley, Chichester
31. [HerediCaRe: Documentation and IT Solution of a Specialized Registry for Hereditary Breast and Ovarian Cancer].
- Author
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Engel C, Wieland K, Zachariae S, Bucksch K, Enders U, Schoenwiese U, Yahiaoui-Doktor M, Keupp K, Waha A, Hahnen E, Remy R, Ernst C, Loeffler M, and Schmutzler RK
- Subjects
- Female, Germany, Humans, Registries, Software, Documentation, Ovarian Neoplasms genetics
- Abstract
The national registry "HerediCaRe" for the evaluation and improvement of risk-adjusted prevention in hereditary breast and ovarian cancer is one of six "model registries in health services research" funded by the BMBF. In this paper, we describe and discuss the documentation and IT solution chosen for standardized data collection based on the specific functional requirements previously defined. The documentation is divided into different modules to be used individually for each patient, which are based on a previously defined catalog of documentation items. Due to special functional requirements, a specific data entry application based on ORACLE and ORACLE Forms was developed and implemented. The specific requirements included the integration of graphical pedigree representations, the structured upload of pedigree data and molecular genetic information, the automated transfer of old data from the previous system, as well as the free programmability of complex database queries for central data quality control. A database for patient-independent management of genetic risk variants was seamlessly integrated into the application and linked to the patient-related data. The advantages and disadvantages of the chosen IT solution are critically discussed. Overall, we come to the conclusion that, in view of the complex documentation and the special functional requirements, there are no alternative ready-made software products to the in-house development we have chosen., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2021
- Full Text
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