Citations 5
Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification
Brünger, Tobias , Krey, Ilona , Kim, Suyeon, Klöckner, Chiara , Myers, Scott J, Johannesen, Katrine M. , Stefanski, Arthur , Taylor, Gary, Macnee, Marie , Dahl, Rebekka S., Yuan, Hongjie, Kim, Sukhan, Helbig, Ingo, Pan, Jen, Kurganov, Erkin , Baez, David, Zuberi, Sameer M., Lerche, Holger, May, Patrick, Ivaniuk, Alina, Meskis, Mary Anne , Hood, Veronica , Schust, Leah F., Freed, Amber, Froelich, Steven, Deng, Alexander T., Bouman, Arjan , Hajianpour, M.J. , Pal, Deb K. , Danvoye, Leslie, Lederer, Damien , BALCI, TUĞÇE, Hagebeuk, Eveline , Heidlebaugh, Alexis R. , Oetjens, Kathryn F., Striano, Pasquale, Williams, Sarah Drewes, Engelen, Kalene van , Howell, Katherine B. , Khoury, Jean , Benke, Tim A., Strehlow, Vincent , Platzer, Konrad, Ramsey, Amy J, Manaster, Lisa, Malepati, Sunitha, Fox, Pangkong M., Noebels, Jeffrey, Chung, Wendy, Poduri, Annapurna, Stripe, Laina Lusk, Ruggiero, Sarah M., Cohen, Stacey, Wilmarth, Olivia, Prentice, Anna Jenne, Cha, Esther, Budnik, Nikita , Kramer, Audra A. , Gh, Zhang, Palotie, Aarno, Daly, Mark J., Møller, R., Lemke, Johannes R., Lal, Dennis , Møller, Rikke S. , May, Patrick , Bruenger, Tobias , Pan, Jen Q , Farrant, Mark , Wyllie, David J A , Bosselmann, Christian , Mantegazza, Massimo , May, Patrick , Ivaniuk, Alina , Goodspeed, Kimberly , Trinidad, Marena , Aledo-Serrano, Ángel , Pal, Deb K , Platzer, Konrad , Ruggiero, Sarah M , Daly, Mark J. , George, Alfred L , Brunklaus, Andreas , Møller, Rikke S , Myers, Scott J. , Taylor, Gary, Pérez‐Palma, Eduardo , Schorge, Stéphanie , Dahl, Rebekka S. , Perszyk, Riley E. , Bajaj, Sunanjay , Helbig, Ingo , Wollmuth, Lonnie P. , Báez-Nieto, David , Zuberi, Sameer M. , Boßelmann, Christian M. , Mantegazza, Massimo , Cestèle, Sandrine , Ivaniuk, Alina , Kang, Jing‐Qiong , Gati, Cornelius , Montanucci, Ludovica , Wüster, Arthur , Deng, Alexander T. , Borovikov, Artem O. , Sharkov, Artem A. , Bouman, Arjan , Hoffman, Trevor L. , Howell, Katherine B. , Benke, Tim A. , Platzer, Konrad , Ramsey, Amy J. , Fox, Pangkong , Noebels, Jeffrey L. , Chung, Wendy K. , Poduri, Annapurna , Lusk, Laina G. , Cohen, Stacey , Smith, Lacey A. , Boesch, Sylvia , Prentice, Anna Jenne , Hommersom, Marina P. , Vanoye, Carlos G. , Nothnagel, Michael , Palotie, Aarno V. , George, Alfred L. , Zárate, Yuri A. , Brunklaus, Andreas , Traynelis, Stephen F. , Lemke, Johannes R.
No container title available | March 6, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface integrates this unified evidence with VCEP-refined ACMG specifications to enable automated gene-specific variant classification, infer molecular mechanisms, and support cross-gene analyses. We demonstrate the framework’s utility across five Gene portals spanning eleven neurodevelopmental disorder-associated genes, integrating data from 4,423 individuals with 2,838 unique variants, 36,149 ClinVar submissions, and 1,044 expert-curated molecular readouts. By organizing evidence that is otherwise dispersed across multiple sources into a unified, queryable framework, the SCN, GRIN, CACNA1A, SATB2 and SLC6A1 Gene Portals became widely used community resources and provide an extensible template for standardized rare-disease variant interpretation and mechanism-aware discovery.
Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Patel, Vivek , Busch, Evan L. , Cronin, Angel M., Leslie, Goska , McGuffog, Lesley, Adlard, Julian , Agata, Simona , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Arason, Aðalgeir , Artioli, Grazia, Arver, Brita, Auber, Bernd , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barroso, Alicia, Barrowdale, Daniel , Belotti, Muriel, Bertelsen, Birgitte , Blok, Marinus J. , Bodrogi, I., Bonadona, Valérie, Bondavalli, Davide , Boonen, Susanne E. , Borde, Julika , Borg, Åke , Bradbury, Angela R. , Brady, Angela, Brewer, Carole, Brunet, Joan , Buecher, Bruno , Caldés, Trinidad , Caliebe, Almuth , Calvello, Mariarosaria , Carrasco, Estela , Chan, Tsun Leung , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Daly, Mary B., Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Puppa, Lara Della , Ding, Yuan Chun , Ditsch, Nina , Donaldson, Alan, Dworniczak, Bernd , Easton, Douglas F. , Eccles, Diana M., Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , Engel, Christoph , Evans, D. Gareth , Faivre, Laurence, Faust, Ulrike , Feliubadaló, Lídia , Foretová, Lenka , Fountzilas, George , Frost, Debra, García‐Barberán, Vanesa , Gauthier‐Villars, Marion , Géczi, Lajos , Gehrig, Andrea, Gesta, Paul , Giannini, Giuseppe , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hamann, Ute, Hauke, Jan , Herold, Natalie, Hogervorst, Frans B.L., Honisch, Ellen, Hulick, Peter J. , Investigators, kConFab, Investigators, Hebon, Izatt, Louise , Jager, Agnes , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Jensen, Thomas D., Johannsson, Oskar T., John, Esther M. , Kang, Eunyoung , Kast, Karin, Kiiski, Johanna I. , Kim, Sung-Won, Ko, Kwang‐Pil , Konstantopoulou, Irene , Kramer, Gero , Krogh, Lotte, Kruse, Torben A., Kwong, Ava , Larsen, Mirjam, Lasset, Christine , Lautrup, Charlotte Kvist , Lee, Jihyoun , Lee, Jong Won, Lee, Min Hyuk , Lesueur, Fabienne , Liljegren, Annelie , Lindblom, Annika , Llovet, Patricia , López‐Fernández, Adrià , López‐Perolio, Irene, Lorca, Víctor , Loud, Jennifer T. , S.K., Edmond , Mai, Phuong L., Manoukian, Siranoush , Mari, Véronique , Martin, Lynn , Matricardi, Laura , Mebirouk, Noura, Medici, Veronica, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Miller, Clare , Gomes, D. Molina , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Navrátilová, Marie , Niederacher, Dieter , Nielsen, Finn C., Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Ong, Kai-Ren, Osório, Ana , Ott, Claus‐Eric , Park, Sue K. , Pedersen, Inge Søkilde , Peissel, Bernard , Peixoto, Ana , Peterlongo, Paolo , Petersen, Annabeth Høgh , Porteous, Mary, Pujana, Miguel Ángel , Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rizzolo, Piera , Rookus, Matti A. , Rossing, Caroline Maria, Ruddy, Kathryn J. , Santos, Catarina , Saule, Claire , Scarpitta, Rosa , Schmutzler, Rita K., Schuster, Hélène, Senter, Leigha , Seynaeve, Caroline, Shah, Payal D. , Silvestri, Valentina , Simard, Jacques , Skytte, Anne‐Bine , Snape, Katie , Solano, Ángela R. , Soucy, Penny, Sunde, Lone , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Thomassen, Mads , Tibiletti, Maria Grazia , Toland, Amanda Ewart, Torres, Diana , Trainer, Alison H., Baan, Frederieke H. van der , Kolk, Lizet E. van der, Hest, Liselotte P. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Viel, Alessandra , Vierstraete, Jeroen , Villa, Roberta, Wachenfeldt, Anna von , Wagner, Philipp , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Wieme, Greet , Yadav, Siddhartha , Yoon, Sook‐Yee , Zanzottera, Cristina , Zorn, Kristin K. , D’Amico, Anthony V. , Freedman, Matthew L. , Pomerantz, Mark M., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Ottini, Laura , Nielsen, Henriette Roed, Durocher, Francine , Eccles, Diana , Caputo, Sandrine M. , Faivre, Laurence , Leslie, Goska , Adlard, Julian , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barnes, Daniel R , Brunet, Joan , Caligo, Maria A , Campbell, Ian G , Claes, Kathleen B M , Darder, Esther , Dennis, Joe , Dworniczak, Bernd , Eeles, Rosalind A , Ehrencrona, Hans , Ejlertsen, Bent , Evans, D Gareth , Garre, Pilar , Greene, Mark H , Hulick, Peter J , Jager, Agnes , James, Paul , John, Esther M , Joseph, Vijai , Kim, Sung-Won , Konstantopoulou, Irene , Lesueur, Fabienne , Matricardi, Laura , Gomes, Denise Molina , Nevanlinna, H , Olopade, Olufunmilayo I , Palli, Domenico , Park, Sue K , Parsons, Michael T , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pujana, Miquel Angel , Ruddy, Kathryn J , Scarpitta, Rosa , Shah, Payal D , Silvestri, Valentina , Southey, Melissa C , Spurdle, Amanda B , Stoppa-Lyonnet, Dominique , Sunde, Lone , Teixeira, Manuel R , Teo, Soo H , Tommasi, Stefania , Toss, Angela , van der Luijt, Rob B , Vierstraete, Jeroen , Wieme, Greet , Yadav, Siddhartha , Antoniou, Antonis C , Eccles, Diana , Weitzel, Jeffrey N , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Boonen, Susanne E , Cortesi, Laura , Engel, Christoph , Hahnen, Eric , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Senter, Leigha , Faivre, Laurence , Rashid, Muhammad U , Calvello, Mariarosaria , Feliubadaló, Lidia , Hauke, Jan , Manoukian, Siranoush , Pomerantz, Mark M , Kwong, Ava , Lindblom, Annika , Friebel, Tara M. , Arnold, Norbert , Balmañà, Judith , Barnes, Daniel R. , Benı́tez, Javier , Bonadona, Valérie , Bonanni, Bernardo , Borg, Åke , Buys, Saundra S. , Cabezas-Camarero, Santiago , Caligo, Maria A. , Campbell, Ian , Carnevali, Ileana Wanda , Chu, Annie Tsz-Wai , Chung, Wendy K. , Cook, Jackie A , Couch, Fergus J. , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Fostira, Florentia , Gerdes, Anne‐Marie , Godwin, Andrew K. , Herold, Natalie, Hopper, John L. , Jensen, Thomas Dyrso, Vijai, Joseph , Lasset, Christine , Lázaro, Conxi , Lemke, Johannes R. , Mai, Phuong L., Meindl, Alfons , Miller, Clare, Moserle, Lidia , Mulligan, Anna Marie , Nevanlinna, Heli , Palli, Domenico , Parsons, Michael T. , Perez-Segura, Pedro , Radice, Paolo , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Shin, Vivian Yvonne , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Steele, Linda, Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Stradella, Agostina , Tischkowitz, Marc D. , Tognazzo, Silvia , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Luijt, Rob B. van der , Yannoukakos, Drakoulis , Neuhausen, Susan L. , Rebbeck, Timothy R.
Cancer Research | November 13, 2019 | Volume: 80 | Issue: 3 | Pages: 624-638
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
HCN1mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond
Marini, Carla , Porro, Alessandro , Rastetter, Agnès, Dalle, Carine, Rivolta, Ilaria , Bauer, Daniel , Oegema, Renske , Nava, Caroline , Parrini, Elena , Mei, Davide , Mercer, Catherine , Dhamija, Radhika , Chambers, Chelsea , Coubes, Christine, Kuentz, Paul , Julia, Sophie , Pasquier, Laurent , Dubourg, Christèle , Carré, Wilfrid , Melani, Federico , Giardino, Maria , Innes, A. Micheil , Alembik, Yves, Scheidecker, Sophie , Figueiroa, Sónia, Garrido, Cristina , Fusco, Carlo , Spagnoli, Carlotta , Binda, Anna , Granata, Tiziana , Ragona, Francesca , Freri, Elena , Franceschetti, Silvana , Canafoglia, Laura , Castellotti, Barbara , Gellera, Cinzia , Milanesi, Raffaella , Mancardi, Maria Margherita , Clark, Damien R, Helbig, Katherine L. , Ichikawa, Shoji , Sadler, Laurie S. , Neupauerová, Jana, Laššuthová, Petra , Štěrbová, Katalin , Laridon, Annick, Brilstra, Eva H. , Koeleman, Bobby P.C. , Striano, Pasquale, Soblet, Julie , Deconinck, Nicolas , Leguern, Éric , Guerrini, Renzo , Santoro, Bina , Hamacher, Kay , Moroni, Anna , DiFrancesco, Jacopo C. , Depienne, Christel , Guerrini, Renzo , Mei, Davide , Pasquier, Laurent , Thévenon, Julien , Rosati, Anna Maria , Pisano, Tiziana , Santos, Manuela M. , Frattini, Daniele , Clark, Damien R., Kok, Fernando , Lemke, Johannes R. , Zara, Federico , Smits, Guillaume , Barbuti, Andrea , DiFrancesco, Dario , Thiel, Gerhard , Depienne, Christel , Dhamija, Radhika
Brain | September 26, 2018 | Volume: 141 | Issue: 11 | Pages: 3160-3178
Clinical spectrum and genotype–phenotype associations of KCNA2-related encephalopathies
Masnada, Silvia , Gardella, Elena , Schubert, Julian , Kaiwar, Charu , Klee, Eric W. , Lanpher, Brendan C. , Gavrilova, Ralitza H. , Synofzik, Matthis , Bast, Thomas , Gorman, Kathleen M. , King, Mary D. , Allen, Nicholas M. , Conroy, Judith, Zeev, Bruria Ben , Tzadok, Michal , Korff, Christian , Dubois, Fanny, Ramsey, Keri , Serratosa, José M. , Giráldez, Beatriz G. , Bergqvist, Christina A , Binelli, Adrian , Zaeyen, Eduardo José Bernardo, Wolff, Markus , Marjanović, Dragan , Çağlayan, Hande, Pena, Sérgio D.J. , Balestrini, Simona , Syrbe, Steffen , Møller, Rikke S. , Rubboli, Guido , Hedrich, Ulrike B. S. , Narayanan, Vinodh , Helbig, Ingo , Marsh, Eric D. , O'Brien, Margaret M. , Porter, Brenda E. , Horovitz, Dafne Dain Gandelman , Arslan, Mutluay , Sisodiya, Sanjay , Veggiotti, Pierangelo , Lemke, Johannes R. , Lerche, Holger , Serratosa, José M , Gorman, Kathleen M , Rubboli, Guido , Synofzik, Matthis , Balestrini, Simona , Gardella, Elena , Møller, Rikke S
Brain | June 29, 2017 | Volume: 140 | Issue: 9 | Pages: 2337-2354
Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders
Wolff, Markus , Johannesen, Katrine M. , Hedrich, Ulrike B. S. , Masnada, Silvia , Rubboli, Guido , Gardella, Elena , Lesca, Gaëtan , Ville, Dorothée , Milh, Mathieu , Villard, Laurent , Afenjar, Alexandra , Chantot‐Bastaraud, Sandra , Mignot, Cyril , Lardennois, Caroline, Nava, Caroline , Schwarz, Niklas , Gérard, Marion , Perrin, Laurence, Doummar, Diane , Miranda, María J., Hempel, Maja , Brilstra, Eva H. , Knoers, Nine, Verbeek, Nienke E., Kempen, Marjan van, Braun, Kees P. J. , Mancini, Grazia M.S. , Biskup, Saskia, Hörtnagel, Konstanze , Döcker, Miriam, Bast, Thomas , Loddenkemper, Tobias , Baumeister, Friedrich, Fazeli, Walid , Striano, Pasquale, Dilena, Robertino , Fontana, Elena , Zara, Federico , Kurlemann, Gerhard, Klepper, Joerg , Thoene, Jess G. , Arndt, Daniel H. , Deconinck, Nicolas , Schmitt‐Mechelke, Thomas , Muhle, Hiltrud, Wical, Beverly, Finetti, C., Brückner, Reinhard , Pietz, Joachim, Golla, G., Jillella, Dinesh , Linnet, Karen Markussen, Charles, Perrine , Moog, Ute , Õiglane‐Shlik, Eve, Mantovani, John F., Park, Kristen , Deprez, Marie, Lederer, Damien , Mary, Sandrine, Scalais, Emmanuel , Selim, Laila , Coster, Rudy Van , Lagae, Lieven , Nikanorova, Marina , Hjalgrim, Helle , Korenke, Georg-Christoph , Trivisano, Marina , Specchio, Nicola , Ceulemans, Berten , Dorn, Thomas, Helbig, Katherine L. , Hardies, Katia, Stamberger, Hannah , Jonghe, Peter De, Weckhuysen, Sarah , Kluger, Gerhard , Møller, Rikke S. , Wong-Kisiel, Lily, Auvin, Stéphane , Kempen, Marjan J. A. van, Wong‐Kisiel, Lily C. , Maier, Oliver , Lemke, Johannes R. , Krägeloh‐Mann, Ingeborg , Helbig, Ingo , Lerche, Holger , Loddenkemper, Tobias , Villard, Laurent , Rubboli, Guido , Schwarz, Niklas , Specchio, Nicola , Gardella, Elena , Lesca, Gaetan , Møller, Rikke S , Jillella, Dinesh V
Brain | February 23, 2017 | Volume: 140 | Issue: 5 | Pages: 1316-1336