351 results on '"Leppig, Kathleen A."'
Search Results
2. O’Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum
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Velmans, Clara, O'Donnell-Luria, Anne H, Argilli, Emanuela, Mau-them, Frederic Tran, Vitobello, Antonio, Chan, Marcus CY, Fung, Jasmine Lee-Fong, Rech, Megan, Abicht, Angela, Mucca, Marion Aubert, Carmichael, Jason, Chassaing, Nicolas, Clark, Robin, Coubes, Christine, Denommé-Pichon, Anne-Sophie, de Dios, John Karl, England, Eleina, Funalot, Benoit, Gerard, Marion, Joseph, Maries, Kennedy, Colleen, Kumps, Camille, Willems, Marjolaine, van de Laar, Ingrid MBH, Aarts-Tesselaar, Coranne, van Slegtenhorst, Marjon, Lehalle, Daphné, Leppig, Kathleen, Lessmeier, Lennart, Pais, Lynn S, Paterson, Heather, Ramanathan, Subhadra, Rodan, Lance H, Superti-Furga, Andrea, Chung, Brian HY, Sherr, Elliott, Netzer, Christian, Schaaf, Christian P, and Erger, Florian
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Human Genome ,Autism ,Mental Health ,Neurosciences ,Clinical Research ,Congenital Structural Anomalies ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Autism Spectrum Disorder ,Child ,Humans ,Intellectual Disability ,Megalencephaly ,Neurodevelopmental Disorders ,Seizures ,Syndrome ,Exome Sequencing ,human genetics ,genetic counselling ,genetics ,behavioural ,mutation ,Medical and Health Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
BackgroundO'Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O'Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.
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- 2022
3. Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing
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Linder, Jodell E., Tao, Ran, Chung, Wendy K., Kiryluk, Krzysztof, Liu, Cong, Weng, Chunhua, Connolly, John J., Hakonarson, Hakon, Harr, Margaret, Leppig, Kathleen A., Jarvik, Gail P., Veenstra, David L., Aufox, Sharon, Chisholm, Rex L., Gordon, Adam S., Hoell, Christin, Rasmussen-Torvik, Laura J., Smith, Maureen E., Holm, Ingrid A., Miller, Erin M., Prows, Cynthia A., Elskeally, Omar, Kullo, Iftikhar J., Lee, Christopher, Jose, Sheethal, Manolio, Teri A., Rowley, Robb, Padi-Adjirackor, Nana Addo, Wilmayani, Ni Ketut, City, Brittany, Wei, Wei-Qi, Wiesner, Georgia L., Rahm, Alanna Kulchak, Williams, Janet L., Williams, Marc S., and Peterson, Josh F.
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- 2023
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4. Using Protection Motivation Theory to Predict Intentions for Breast Cancer Risk Management: Intervention Mechanisms from a Randomized Controlled Trial
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Conley, Claire C., Wernli, Karen J., Knerr, Sarah, Li, Tengfei, Leppig, Kathleen, Ehrlich, Kelly, Farrell, David, Gao, Hongyuan, Bowles, Erin J. A., Graham, Amanda L., Luta, George, Jayasekera, Jinani, Mandelblatt, Jeanne S., Schwartz, Marc D., and O’Neill, Suzanne C.
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- 2023
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5. Returning integrated genomic risk and clinical recommendations: The eMERGE study
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Gordon, Adam, Sobowale, Agboade, Allworth, Aimee, Patel, Akshar, DiVietro, Alanna, Strong, Alanna, Sherafati, Alborz, Sherfati, Alborz, Bick, Alex, Miller, Alexandra, Chandel, Alka, Rosenthal, Alyssa, Khera, Amit, Kontorovich, Amy, Beck, Andrew, Beck, Andy, Espinoza, Angelica, Lewis, Anna, Prince, Anya, Khan, Atlas, Iverson, Ayuko, Khales, Bahram Namjou, Benoit, Barbara, Hernan, Becca, Kallman, Ben, Kerman, Ben, Shoemaker, Ben, Satterfield, Benjamin, Devine, Beth, Etheridge, Bethany, Goff, Blake, Freimuth, Bob, Grundmeier, Bob, Collier, Brenae, Mutai, Brenda, Harnett, Brett, Chang, Brian, Piening, Brian, Davis, Brittney, Korf, Bruce, Patterson, Candace, Demetriou, Carmen, Ta, Casey, Hammack, Catherine, Nelson, Catrina, Gascoigne, Caytie, Dorn, Chad, Moretz, Chad, Kachulis, Chris, Hoell, Christie, Cowles, Christine, Lange, Christoph, Weng, Chunhua, Prows, Cindy, Brokamp, Cole, Liu, Cong, Scherr, Courtney, Gonzalez, Crystal, Ramirez, Cynthia, Shimbo, Daichi, Roden, Dan, Schaid, Daniel, Kaufman, Dave, Crosslin, David, Kochan, David, Veenstra, David, Singh, Davinder, Karavite, Dean, Abrams, Debbie, Absher, Devin, Edwards, Digna Velez, Haverfield, Eden, Morales, Eduardo, Esplin, Edward, Malolepsza, Edyta, Alipour, Ehsan, Kenny, Eimear, Rosenthal, Elisabeth, Duvall, Eliza, McNally, Elizabeth, Bhoj, Elizabeth, Cohn, Elizabeth, Hibler, Elizabeth, Karlson, Elizabeth, Clayton, Ellen, Chesnut, Emily, DeFranco, Emily, Gallagher, Emily, Soper, Emily, Perez, Emma, Cash, Erin, Berner, Eta, Wang, Fei, Wehbe, Firas, Ricci, Francisco, Mentch, Frank, Shaibi, Gabriel, Jarvik, Gail, Hahn, George, Hripcsak, George, Wiesner, Georgia, Belbin, Gillian, Davogustto, Gio, Nadkarni, Girish, Qiu, Haijun, Hakonarson, Hakon, Bangash, Hana, Beasley, Hannah, Liu, Hao, Aungst, Heide, Tiwari, Hemant, Duckham, Hillary, Thomas, Hope, Kullo, Iftikhar, Holm, Ingrid, Allen, Isabelle, Ionita-Laza, Iuliana, Hellwege, Jacklyn, Petrzelka, Jacob, Odgis, Jacqueline, Narula, Jahnavi, Petrzelka, Jake, Patel, Jalpa, Cimino, James, Meigs, James, Snyder, James, Olson, Janet, Zahner, Janet, Pennington, Jeff, Pacheco, Jen, Pacheco, Jennifer Allen, Morse, Jennifer, Corsmo, Jeremy, Thayer, Jeritt, Cimino, Jim, Chen, Jingheng, Fournier, Jocelyn, Jackson, Jodell, Glessner, Joe, Pacyna, Joel, Smith, Johanna, Connolly, John, Lynch, John, Shelley, John, Mosley, Jonathan, Nestor, Jordan, Smoller, Jordan, Alsip, Jorge, Kannry, Joseph, Sutton, Joseph, Peterson, Josh, Smith, Joshua, Galasso, Julia, Smith, Julia, Wynn, Julia, Gundelach, Justin, Starren, Justin, Choi, Karmel, Mittendorf, Kate, Anderson, Katherine, Bonini, Katherine, Leppig, Kathleen, Muenzen, Kathleen, Larkin, Katie, Stuttgen, Kelsey, Wiley, Ken, Nguyen, Kenny, Dufendach, Kevin, Atkins, Kiley, Sawicki, Konrad, Norland, Kristjan, Kiryluk, Krzysztof, Beskow, Laura, Rasmussen-Torvik, Laura, Kottyan, Leah, Hsu, Li, Tian, Lifeng, Mahanta, Lisa, Martin, Lisa, Wang, Lisa, Gomez, Lizbeth, Thompson, Lorenzo, Orlando, Lori, Richter, Lucas, Rasmussen, Luke, Petukhova, Lynn, Seabolt, Lynn, O’Brien, Madison, Harden, Maegan, Fullerton, Malia, Harr, Margaret, Beasley, Mark, Guindo, Marta, Horike, Martha, Horike-Pyne, Martha, Abdalla, Marwah, Hamed, Marwan, Terry, Mary Beth, Maradik, Mary, Wyatt, Matt, Davis, Matthew, Lebo, Matthew, Smith, Maureen, Rosario, Maya del, Sabatello, Maya, Behr, Meckenzie, Roy-Puckelwartz, Meg, Habrat, Mel, Myers, Melanie, Yetisgen, Meliha, Iris, Merve, DaSilva, Michael, Preuss, Michael, McGowan, Michelle, Shi, Mingjian, Perera, Minoli, Thomas, Minta, Elkind, Mitch, Abbass, Mohammad, Saadatagah, Mohammad, Hess, Molly, Maradik, Molly, Vaitinadin, Nataraja “RJ”, Vaitinadin, Nataraja, Muthu, Naveen, Netherly, Neil, Lennon, Niall, Shang, Ning, Limdi, Nita, Forrest, Noah, Romero, Noheli, Robinson, Nora, Abul-Husn, Noura, Elsekaily, Omar, Dikilitas, Ozan, Kovatch, Patricia, Davis, Patrick, Appelbaum, Paul, Francaviglia, Paul, O’Reilly, Paul, Chandler, Paulette, Caraballo, Pedro, Tarczy-Hornoch, Peter, Shum, Pierre, Marathe, Priya, Murali, Priyanka, Feng, Qiping, Wells, Quinn, Atchley, Rachel, Narla, Radhika, Barton, Rene, Sterling, Rene, Chisholm, Rex, Green, Richard, Sharp, Richard, Peters, Riki, Kukafka, Rita, Rowley, Robb, Freimuth, Robert, Green, Robert, Winter, Robert, Mueller, Roger, Loos, Ruth, Irvin, Ryan, Suckiel, Sabrina, Hussain, Sajjad, Sharba, Samer, Aronson, Sandy, Jones, Sarah, Knerr, Sarah, Nigbur, Scott, Weiss, Scott, Mooney, Sean, Terek, Shannon, Aufox, Sharon, Nirenberg, Sharon, Murphy, Shawn, O’Byrne, Sheila, Wang (Sam) Choi, Shing, Aguilar, Sienna, Bland, S.T., Rodrigues, Stefanie, Ledbetter, Stephanie, Rutledge, Stephanie, Booth, Stuart James, Xian, Su, Trinidad, Susan Brown, Bakken, Suzanne, Schmidlen, Tara, Rakhra-Burris, Tejinder, Manolio, Teri, Mersha, Tesfaye, Walunas, Theresa, Chandereng, Thevaa, May, Thomas, Ge, Tian, Edwards, Todd, Kaszemacher, Tom, Hernandez, Valentina, Willis, Valerie, Desai, Vemi, Desai, Vimi, Lorenzi, Virginia, Gainer, Vivian, Wei, Wei-Qi, Chung, Wendy, Su, Wu-Chen, Chang, Xiao, Zhao, Yiqing, Luo, Yuan, Shen, Yufeng, Linder, Jodell E., Bland, Harris T., Caraballo, Pedro J., Chisholm, Rex L., Clayton, Ellen Wright, Crosslin, David R., Esplin, Edward D., Forman, Sophie, Freimuth, Robert R., Gordon, Adam S., Harden, Maegan V., Holm, Ingrid A., Jarvik, Gail P., Karlson, Elizabeth W., Labrecque, Sofia, Lennon, Niall J., Limdi, Nita A., Mittendorf, Kathleen F., Murphy, Shawn N., Prows, Cynthia A., Rasmussen, Luke V., Sawicki, Konrad Teodor, Velez Edwards, Digna R., Abul-Husn, Noura S., Below, Jennifer E., Berner, Eta S., Booth, James, Chung, Wendy K., Cimino, James J., Fullerton, Stephanie M., Guiducci, Candace, Habrat, Melissa L., Hain, Heather, Hoell, Christin, Irvin, Marguerite R., Kachulis, Christopher, Kenny, Eimear E., Kullo, Iftikhar J., Manolio, Teri A., McNally, Elizabeth M., Mooney, Sean D., Namjou, Bahram, Perez, Emma F., Puckelwartz, Megan J., Roden, Dan M., Rosenthal, Elisabeth A., Saadatagah, Seyedmohammad, Schaid, Dan J., Schultz, Baergen, Shaibi, Gabriel Q., Sharp, Richard R., Shirts, Brian, Smith, Maureen E., Smoller, Jordan W., Suckiel, Sabrina A., Tiwari, Hemant K., Trinidad, Susan B., Wells, Quinn S., Wiesner, Georgia L., and Peterson, Josh F.
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- 2023
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6. The FamilyTalk randomized controlled trial : patient-reported outcomes in clinical genetic sequencing for colorectal cancer
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Makhnoon, Sukh, Bowen, Deborah J., Shirts, Brian H., Fullerton, Stephanie M., Larson, Eric B., Ralston, James D., Leppig, Kathleen A., Crosslin, David R., Veenstra, David, and Jarvik, Gail P.
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- 2021
7. Impact of returning unsolicited genomic results to nongenetic health care providers in the eMERGE III Network
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Madden, Jill A., Brothers, Kyle K., Williams, Janet L., Myers, Melanie F., Leppig, Kathleen A., Clayton, Ellen Wright, Wiesner, Georgia L., and Holm, Ingrid A.
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- 2022
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8. The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network
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Leppig, Kathleen A., Kulchak Rahm, Alanna, Appelbaum, Paul, Aufox, Sharon, Bland, Harris T., Buchanan, Adam, Christensen, Kurt D., Chung, Wendy K., Clayton, Ellen Wright, Crosslin, David, Denny, Josh, DeVange, Shannon, Gordon, Adam, Green, Robert C., Hakonarson, Hakon, Harr, Margaret H., Henrikson, Nora, Hoell, Christin, Holm, Ingrid A., Kullo, Iftikhar J., Jarvik, Gail P., Lammers, Philip E., Larson, Eric B., Lindor, Noralane M., Marasa, Maddalena, Myers, Melanie F., Perez, Emma, Peterson, Josh F., Pratap, Siddharth, Prows, Cynthia A., Ralston, James D., Rasouly, Hila Milo, Roden, Dan M., Sharp, Richard R., Singh, Rajbir, Shaibi, Gabriel, Smith, Maureen E., Sturm, Amy, Thiese, Heidi A., Van Driest, Sara L., Williams, Janet, Williams, Marc S., Wynn, Julia, Blout Zawatsky, Carrie L., and Wiesner, Georgia L.
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- 2022
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9. Reanalysis of eMERGE phase III sequence variants in 10,500 participants and infrastructure to support the automated return of knowledge updates
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Zouk, Hana, Yu, Wanfeng, Oza, Andrea, Hawley, Megan, Vijay Kumar, Prathik K., Koch, Christopher, Mahanta, Lisa M., Harley, John B., Jarvik, Gail P., Karlson, Elizabeth W., Leppig, Kathleen A., Myers, Melanie F., Prows, Cynthia A., Williams, Marc S., Weiss, Scott T., Lebo, Matthew S., and Rehm, Heidi L.
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- 2022
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10. Feasibility, acceptability, and limited efficacy of health system-led familial risk notification: protocol for a mixed-methods evaluation
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Blasi, Paula R., Scrol, Aaron, Anderson, Melissa L., Gray, Marlaine Figueroa, Tiffany, Brooks, Fullerton, Stephanie M., Ralston, James D., Leppig, Kathleen A., and Henrikson, Nora B.
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- 2022
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11. Neptune: an environment for the delivery of genomic medicine
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Eric, Venner, Yi, Victoria, Murdock, David, Kalla, Sara E., Wu, Tsung-Jung, Sabo, Aniko, Li, Shoudong, Meng, Qingchang, Tian, Xia, Murugan, Mullai, Cohen, Michelle, Kovar, Christie, Wei, Wei-Qi, Chung, Wendy K., Weng, Chunhua, Wiesner, Georgia L., Jarvik, Gail P., Muzny, Donna, Gibbs, Richard A., Abrams, Debra, Adunyah, Samuel E., Albertson-Junkans, Ladia, Almoguera, Berta, Ames, Darren C., Appelbaum, Paul, Aronson, Samuel, Aufox, Sharon, Babb, Lawrence J., Balasubramanian, Adithya, Bangash, Hana, Basford, Melissa, Bastarache, Lisa, Baxter, Samantha, Behr, Meckenzie, Benoit, Barbara, Bhoj, Elizabeth, Bielinski, Suzette J., Bland, Harris T., Blout, Carrie, Borthwick, Kenneth, Bottinger, Erwin P., Bowser, Mark, Brand, Harrison, Brilliant, Murray, Brodeur, Wendy, Caraballo, Pedro, Carrell, David, Carroll, Andrew, Castillo, Lisa, Castro, Victor, Chandanavelli, Gauthami, Chiang, Theodore, Chisholm, Rex L., Christensen, Kurt D., Chung, Wendy, Chute, Christopher G., City, Brittany, Cobb, Beth L., Connolly, John J., Crane, Paul, Crew, Katherine, Crosslin, David R., Dayal, Jyoti, De Andrade, Mariza, De la Cruz, Jessica, Denny, Josh C., Denson, Shawn, DeSmet, Tim, Dikilitas, Ozan, Dinsmore, Michael J., Dodge, Sheila, Dunlea, Phil, Edwards, Todd L., Eng, Christine M., Fasel, David, Fedotov, Alex, Feng, Qiping, Fleharty, Mark, Foster, Andrea, Freimuth, Robert, Friedrich, Christopher, Fullerton, Stephanie M., Funke, Birgit, Gabriel, Stacey, Gainer, Vivian, Gharavi, Ali, Glazer, Andrew M., Glessner, Joseph T., Goehringer, Jessica, Gordon, Adam S., Graham, Chet, Green, Robert C., Gundelach, Justin H., Hain, Heather S., Hakonarson, Hakon, Harden, Maegan V., Harley, John, Harr, Margaret, Hartzler, Andrea, Hayes, M. Geoffrey, Hebbring, Scott, Henrikson, Nora, Hershey, Andrew, Hoell, Christin, Holm, Ingrid, Howell, Kayla M., Hripcsak, George, Hu, Jianhong, Hynes, Elizabeth Duffy, Jayaseelan, Joy C., Jiang, Yunyun, Joo, Yoonjung Yoonie, Jose, Sheethal, Josyula, Navya Shilpa, Justice, Anne E., Kalra, Divya, Karlson, Elizabeth W., Keating, Brendan J., Kelly, Melissa A., Kenny, Eimear E., Key, Dustin, Kiryluk, Krzysztof, Kitchner, Terrie, Klanderman, Barbara, Klee, Eric, Kochan, David C., Korchina, Viktoriya, Kottyan, Leah, Kudalkar, Emily, Rahm, Alanna Kulchak, Kullo, Iftikhar J., Lammers, Philip, Larson, Eric B., Lebo, Matthew S., Leduc, Magalie, Lee, Ming Ta (Michael), Lennon, Niall J., Leppig, Kathleen A., Leslie, Nancy D., Li, Rongling, Liang, Wayne H., Lin, Chiao-Feng, Linder, Jodell E., Lindor, Noralane M., Lingren, Todd, Linneman, James G., Liu, Cong, Liu, Wen, Liu, Xiuping, Lynch, John, Lyon, Hayley, Macbeth, Alyssa, Mahadeshwar, Harshad, Mahanta, Lisa, Malin, Bradley, Manolio, Teri, Marasa, Maddalena, Marsolo, Keith, McGowan, Michelle L., McNally, Elizabeth, Meldrim, Jim, Mentch, Frank, Rasouly, Hila Milo, Mosley, Jonathan, Mukherjee, Shubhabrata, Mullen, Thomas E., Muniz, Jesse, Murdock, David R., Murphy, Shawn, Myers, Melanie F., Namjou, Bahram, Ni, Yizhao, Onofrio, Robert C., Obeng, Aniwaa Owusu, Person, Thomas N., Peterson, Josh F., Petukhova, Lynn, Pisieczko, Cassandra J., Pratap, Siddharth, Prows, Cynthia A., Puckelwartz, Megan J., Raj, Ritika, Ralston, James D., Ramaprasan, Arvind, Ramirez, Andrea, Rasmussen, Luke, Rasmussen-Torvik, Laura, Raychaudhuri, Soumya, Rehm, Heidi L., Ritchie, Marylyn D., Rives, Catherine, Riza, Beenish, Roden, Dan M., Rosenthal, Elisabeth A., Santani, Avni, Dan, Schaid, Scherer, Steven, Scott, Stuart, Scrol, Aaron, Sengupta, Soumitra, Shang, Ning, Sharma, Himanshu, Sharp, Richard R., Singh, Rajbir, Sleiman, Patrick M.A., Slowik, Kara, Smith, Joshua C., Smith, Maureen E., Smoot, Duane T., Smoller, Jordan W., Sohn, Sunghwan, Stanaway, Ian B., Starren, Justin, Stroud, Mary, Su, Jessica, Taylor, Casey Overby, Tolwinski, Kasia, Van Driest, Sara L., Vargas, Sean M., Varugheese, Matthew, Veenstra, David, Venner, Eric, Verbitsky, Miguel, Vicente, Gina, Wagner, Michael, Walker, Kimberly, Walunas, Theresa, Wang, Liwen, Wang, Qiaoyan, Weiss, Scott T., Wells, Quinn S., White, Peter S., Wiley, Ken L., Jr, Williams, Janet L., Williams, Marc S., Wilson, Michael W., Witkowski, Leora, Woods, Laura Allison, Woolf, Betty, Wynn, Julia, Yang, Yaping, Zhang, Ge, Zhang, Lan, and Zouk, Hana
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- 2021
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12. Preferences of biobank participants for receiving actionable genomic test results: results of a recontacting study
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Henrikson, Nora B., Scrol, Aaron, Leppig, Kathleen A., Ralston, James D., Larson, Eric B., and Jarvik, Gail P.
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- 2021
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13. DLG4-related synaptopathy: a new rare brain disorder
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Rodríguez-Palmero, Agustí, Boerrigter, Melissa Maria, Gómez-Andrés, David, Aldinger, Kimberly A., Marcos-Alcalde, Íñigo, Popp, Bernt, Everman, David B., Lovgren, Alysia Kern, Arpin, Stephanie, Bahrambeigi, Vahid, Beunders, Gea, Bisgaard, Anne-Marie, Bjerregaard, V.A., Bruel, Ange-Line, Challman, Thomas D., Cogné, Benjamin, Coubes, Christine, de Man, Stella A., Denommé-Pichon, Anne-Sophie, Dye, Thomas J., Elmslie, Frances, Feuk, Lars, García-Miñaúr, Sixto, Gertler, Tracy, Giorgio, Elisa, Gruchy, Nicolas, Haack, Tobias B., Haldeman-Englert, Chad R., Haukanes, Bjørn Ivar, Hoyer, Juliane, Hurst, Anna C.E., Isidor, Bertrand, Soller, Maria Johansson, Kushary, Sulagna, Kvarnung, Malin, Landau, Yuval E., Leppig, Kathleen A., Lindstrand, Anna, Kleinendorst, Lotte, MacKenzie, Alex, Mandrile, Giorgia, Mendelsohn, Bryce A., Moghadasi, Setareh, Morton, Jenny E., Moutton, Sebastien, Müller, Amelie J., O’Leary, Melanie, Pacio-Míguez, Marta, Palomares-Bralo, Maria, Parikh, Sumit, Pfundt, Rolph, Pode-Shakked, Ben, Rauch, Anita, Repnikova, Elena, Revah-Politi, Anya, Ross, Meredith J., Ruivenkamp, Claudia A.L., Sarrazin, Elisabeth, Savatt, Juliann M., Schlüter, Agatha, Schönewolf-Greulich, Bitten, Shad, Zohra, Shaw-Smith, Charles, Shieh, Joseph T., Shohat, Motti, Spranger, Stephanie, Thiese, Heidi, Mau-Them, Frederic Tran, van Bon, Bregje, van de Burgt, Ineke, van de Laar, Ingrid M.B.H., van Drie, Esmée, van Haelst, Mieke M., van Ravenswaaij-Arts, Conny M., Verdura, Edgard, Vitobello, Antonio, Waldmüller, Stephan, Whiting, Sharon, Zweier, Christiane, Prada, Carlos E., de Vries, Bert B.A., Dobyns, William B., Reiter, Simone F., Gómez-Puertas, Paulino, Pujol, Aurora, and Tümer, Zeynep
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- 2021
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14. De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy
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Klöckner, Chiara, Sticht, Heinrich, Zacher, Pia, Popp, Bernt, Babcock, Holly E., Bakker, Dewi P., Barwick, Katy, Bonfert, Michaela V., Bönnemann, Carsten G., Brilstra, Eva H., Chung, Wendy K., Clarke, Angus J., Devine, Patrick, Donkervoort, Sandra, Fraser, Jamie L., Friedman, Jennifer, Gates, Alyssa, Ghoumid, Jamal, Hobson, Emma, Horvath, Gabriella, Keller-Ramey, Jennifer, Keren, Boris, Kurian, Manju A., Lee, Virgina, Leppig, Kathleen A., Lundgren, Johan, McDonald, Marie T., McLaughlin, Heather M., McTague, Amy, Mefford, Heather C., Mignot, Cyril, Mikati, Mohamad A., Nava, Caroline, Raymond, F. Lucy, Sampson, Julian R., Sanchis-Juan, Alba, Shashi, Vandana, Shieh, Joseph T.C., Shinawi, Marwan, Slavotinek, Anne, Stödberg, Tommy, Stong, Nicholas, Sullivan, Jennifer A., Taylor, Ashley C., Toler, Tomi L., van den Boogaard, Marie-José, van der Crabben, Saskia N., van Gassen, Koen L.I., van Jaarsveld, Richard H., Van Ziffle, Jessica, Wadley, Alexandrea F., Wagner, Matias, Wigby, Kristen, Wortmann, Saskia B., Zarate, Yuri A., Møller, Rikke S., Lemke, Johannes R., and Platzer, Konrad
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- 2021
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15. Participant choices for return of genomic results in the eMERGE Network
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Hoell, Christin, Wynn, Julia, Rasmussen, Luke V., Marsolo, Keith, Aufox, Sharon A., Chung, Wendy K., Connolly, John J., Freimuth, Robert R., Kochan, David, Hakonarson, Hakon, Harr, Margaret, Holm, Ingrid A., Kullo, Iftikhar J., Lammers, Philip E., Leppig, Kathleen A., Leslie, Nancy D., Myers, Melanie F., Sharp, Richard R., Smith, Maureen E., and Prows, Cynthia A.
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- 2020
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16. Ethical conflicts in translational genetic research: lessons learned from the eMERGE-III experience
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Halverson, Colin M.E., Bland, Harris T., Leppig, Kathleen A., Marasa, Maddalena, Myers, Melanie, Rasouly, Hila Milo, Wynn, Julia, and Clayton, Ellen Wright
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- 2020
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17. Frequency of genomic secondary findings among 21,915 eMERGE network participants
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Gordon, Adam S., Zouk, Hana, Venner, Eric, Eng, Christine M., Funke, Birgit H., Amendola, Laura M., Carrell, David S., Chisholm, Rex L., Chung, Wendy K., Denny, Joshua C., Fedotov, Alexander, Hakonarson, Hakon, Kullo, Iftikhar J., Larson, Eric B., Leduc, Magalie S., Leppig, Kathleen A., Lennon, Niall J., Linder, Jodell E., Muzny, Donna M., Prows, Cynthia A., Rasmussen-Torvik, Laura J., Rasouly, Hila Milo, Roden, Dan M., Rosenthal, Elisabeth A., Smith, Maureen E., Stanaway, Ian B., Van Driest, Sara L., Walker, Kimberly, Wiesner, Georgia L., Williams, Marc S., Witkowski, Leora, Crosslin, David R., Gibbs, Richard A., Rehm, Heidi L., and Jarvik, Gail P.
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- 2020
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18. Spliceosome malfunction causes neurodevelopmental disorders with overlapping features
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Genetica, Genetica Sectie Research, Cancer, Child Health, Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, Hakonarson, Hakon, Genetica, Genetica Sectie Research, Cancer, Child Health, Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, and Hakonarson, Hakon
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- 2024
19. Spliceosome malfunction causes neurodevelopmental disorders with overlapping features
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Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, Hakonarson, Hakon, Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, and Hakonarson, Hakon
- Abstract
Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function.
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- 2024
20. Developmental epileptic encephalopathy in DLG4-related synaptopathy
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Kassabian, Benedetta, Levy, Amanda M., Gardella, Elena, Aledo-Serrano, Angel, Ananth, Amitha L., Brea-Fernández, Alejandro J., Caumes, Roseline, Chatron, Nicolas, Dainelli, Alice, De Wachter, Matthias, Denommé-Pichon, Anne-Sophie, Dye, Thomas J., Fazzi, Elisa, Felt, Roxanne, Fernández-Jaén, Alberto, Fernández-Prieto, Montse, Gantz, Emily, Gasperowicz, Piotr, Gil-Nagel, Antonio, Gómez-Andrés, David, Greiner, Hansel M., Guerrini, Renzo, Haanpää, Maria K., Helin, Minttu, Hoyer, Juliane, Hurst, Anna C. E., Kallish, Staci, Karkare, Shefali N., Khan, Amjad, Kleinendorst, Lotte, Koch, Johannes, Kothare, Sanjeev V., Koudijs, Suzanna M., Lagae, Lieven, Lakeman, Phillis, Leppig, Kathleen A., Lesca, Gaetan, Lopergolo, Diego, Lusk, Laina, Mackenzie, Alex, Mei, Davide, Møller, Rikke S., Pereira, Elaine M., Platzer, Konrad, Quelin, Chloe, Revah-Politi, Anya, Rheims, Sylvain, Rodríguez-Palmero, Agustí, Rossi, Andrea, Santorelli, Filippo, Seinfeld, Syndi, Sell, Erick, Stephenson, Donna, Szczaluba, Krzysztof, Trinka, Eugen, Umair, Muhammad, Van Esch, Hilde, van Haelst, Mieke M., Veenma, Danielle C. M., Weber, Sacha, Weckhuysen, Sarah, Zacher, Pia, Tümer, Zeynep, Rubboli, Guido, Kassabian, Benedetta, Levy, Amanda M., Gardella, Elena, Aledo-Serrano, Angel, Ananth, Amitha L., Brea-Fernández, Alejandro J., Caumes, Roseline, Chatron, Nicolas, Dainelli, Alice, De Wachter, Matthias, Denommé-Pichon, Anne-Sophie, Dye, Thomas J., Fazzi, Elisa, Felt, Roxanne, Fernández-Jaén, Alberto, Fernández-Prieto, Montse, Gantz, Emily, Gasperowicz, Piotr, Gil-Nagel, Antonio, Gómez-Andrés, David, Greiner, Hansel M., Guerrini, Renzo, Haanpää, Maria K., Helin, Minttu, Hoyer, Juliane, Hurst, Anna C. E., Kallish, Staci, Karkare, Shefali N., Khan, Amjad, Kleinendorst, Lotte, Koch, Johannes, Kothare, Sanjeev V., Koudijs, Suzanna M., Lagae, Lieven, Lakeman, Phillis, Leppig, Kathleen A., Lesca, Gaetan, Lopergolo, Diego, Lusk, Laina, Mackenzie, Alex, Mei, Davide, Møller, Rikke S., Pereira, Elaine M., Platzer, Konrad, Quelin, Chloe, Revah-Politi, Anya, Rheims, Sylvain, Rodríguez-Palmero, Agustí, Rossi, Andrea, Santorelli, Filippo, Seinfeld, Syndi, Sell, Erick, Stephenson, Donna, Szczaluba, Krzysztof, Trinka, Eugen, Umair, Muhammad, Van Esch, Hilde, van Haelst, Mieke M., Veenma, Danielle C. M., Weber, Sacha, Weckhuysen, Sarah, Zacher, Pia, Tümer, Zeynep, and Rubboli, Guido
- Abstract
Objective: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy. Methods: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. Results: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike–wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype–phenotype relationship even between individuals with the same DLG4 variants. Significance: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requi
- Published
- 2024
21. Development of FamilyTalk: an Intervention to Support Communication and Educate Families About Colorectal Cancer Risk
- Author
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Bowen, Deborah J., Hyams, Travis, Laurino, Mercy, Woolley, Timothy, Cohen, Stacey, Leppig, Kathleen A., and Jarvik, Gail
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- 2020
- Full Text
- View/download PDF
22. Actionable exomic incidental findings in 6503 participants: challenges of variant classification
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Amendola, Laura M, Dorschner, Michael O, Robertson, Peggy D, Salama, Joseph S, Hart, Ragan, Shirts, Brian H, Murray, Mitzi L, Tokita, Mari J, Gallego, Carlos J, Kim, Daniel Seung, Bennett, James T, Crosslin, David R, Ranchalis, Jane, Jones, Kelly L, Rosenthal, Elisabeth A, Jarvik, Ella R, Itsara, Andy, Turner, Emily H, Herman, Daniel S, Schleit, Jennifer, Burt, Amber, Jamal, Seema M, Abrudan, Jenica L, Johnson, Andrew D, Conlin, Laura K, Dulik, Matthew C, Santani, Avni, Metterville, Danielle R, Kelly, Melissa, Foreman, Ann Katherine M, Lee, Kristy, Taylor, Kent D, Guo, Xiuqing, Crooks, Kristy, Kiedrowski, Lesli A, Raffel, Leslie J, Gordon, Ora, Machini, Kalotina, Desnick, Robert J, Biesecker, Leslie G, Lubitz, Steven A, Mulchandani, Surabhi, Cooper, Greg M, Joffe, Steven, Richards, C Sue, Yang, Yaoping, Rotter, Jerome I, Rich, Stephen S, O’Donnell, Christopher J, Berg, Jonathan S, Spinner, Nancy B, Evans, James P, Fullerton, Stephanie M, Leppig, Kathleen A, Bennett, Robin L, Bird, Thomas, Sybert, Virginia P, Grady, William M, Tabor, Holly K, Kim, Jerry H, Bamshad, Michael J, Wilfond, Benjamin, Motulsky, Arno G, Scott, C Ronald, Pritchard, Colin C, Walsh, Tom D, Burke, Wylie, Raskind, Wendy H, Byers, Peter, Hisama, Fuki M, Rehm, Heidi, Nickerson, Debbie A, and Jarvik, Gail P
- Subjects
Biological Sciences ,Genetics ,Minority Health ,Genetic Testing ,Health Disparities ,Biotechnology ,Cancer Genomics ,Clinical Research ,Cancer ,Human Genome ,Good Health and Well Being ,Adult ,Black People ,Exome ,Female ,Gene Frequency ,Genes ,Dominant ,Genetic Association Studies ,Genome ,Human ,Genomics ,High-Throughput Nucleotide Sequencing ,Humans ,Incidental Findings ,Male ,Phenotype ,Polymorphism ,Single Nucleotide ,White People ,Medical and Health Sciences ,Bioinformatics - Abstract
Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base.
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- 2015
23. Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network
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Zouk, Hana, Venner, Eric, Lennon, Niall J., Muzny, Donna M., Abrams, Debra, Adunyah, Samuel, Albertson-Junkans, Ladia, Ames, Darren C., Appelbaum, Paul, Aronson, Samuel, Aufox, Sharon, Babb, Lawrence J., Balasubramanian, Adithya, Bangash, Hana, Basford, Melissa, Bastarache, Lisa, Baxter, Samantha, Behr, Meckenzie, Benoit, Barbara, Bhoj, Elizabeth, Bielinski, Suzette J., Bland, Harris T., Blout, Carrie, Borthwick, Kenneth, Bottinger, Erwin P., Bowser, Mark, Brand, Harrison, Brilliant, Murray, Brodeur, Wendy, Caraballo, Pedro, Carrell, David, Carroll, Andrew, Almoguera, Berta, Castillo, Lisa, Castro, Victor, Chandanavelli, Gauthami, Chiang, Theodore, Chisholm, Rex L., Christensen, Kurt D., Chung, Wendy, Chute, Christopher G., City, Brittany, Cobb, Beth L., Connolly, John J., Crane, Paul, Crew, Katherine, Crosslin, David, De Andrade, Mariza, De la Cruz, Jessica, Denson, Shawn, Denny, Josh, DeSmet, Tim, Dikilitas, Ozan, Friedrich, Christopher, Fullerton, Stephanie M., Funke, Birgit, Gabriel, Stacey, Gainer, Vivian, Gharavi, Ali, Glazer, Andrew M., Glessner, Joseph T., Goehringer, Jessica, Gordon, Adam S., Graham, Chet, Green, Robert C., Gundelach, Justin H., Dayal, Jyoti, Hain, Heather S., Hakonarson, Hakon, Harden, Maegan V., Harley, John, Harr, Margaret, Hartzler, Andrea, Hayes, M. Geoffrey, Hebbring, Scott, Henrikson, Nora, Hershey, Andrew, Hoell, Christin, Holm, Ingrid, Howell, Kayla M., Hripcsak, George, Hu, Jianhong, Jarvik, Gail P., Jayaseelan, Joy C., Jiang, Yunyun, Joo, Yoonjung Yoonie, Jose, Sheethal, Josyula, Navya Shilpa, Justice, Anne E., Kalla, Sara E., Kalra, Divya, Karlson, Elizabeth, Kelly, Melissa A., Keating, Brendan J., Kenny, Eimear E., Key, Dustin, Kiryluk, Krzysztof, Kitchner, Terrie, Klanderman, Barbara, Klee, Eric, Kochan, David C., Korchina, Viktoriya, Kottyan, Leah, Kovar, Christie, Kudalkar, Emily, Kullo, Iftikhar J., Lammers, Philip, Larson, Eric B., Lebo, Matthew S., Leduc, Magalie, Lee, Ming Ta (Michael), Leppig, Kathleen A., Leslie, Nancy D., Li, Rongling, Liang, Wayne H., Lin, Chiao-Feng, Linder, Jodell, Lindor, Noralane M., Lingren, Todd, Linneman, James G., Liu, Cong, Liu, Wen, Liu, Xiuping, Lynch, John, Lyon, Hayley, Macbeth, Alyssa, Mahadeshwar, Harshad, Mahanta, Lisa, Malin, Brad, Manolio, Teri, Marasa, Maddalena, Marsolo, Keith, Dinsmore, Michael J., Dodge, Sheila, Hynes, Elizabeth Duffy, Dunlea, Phil, Edwards, Todd L., Eng, Christine M., Fasel, David, Fedotov, Alex, Feng, Qiping, Fleharty, Mark, Foster, Andrea, Freimuth, Robert, McGowan, Michelle L., McNally, Elizabeth, Meldrim, Jim, Mentch, Frank, Mosley, Jonathan, Mukherjee, Shubhabrata, Mullen, Thomas E., Muniz, Jesse, Murdock, David R., Murphy, Shawn, Murugan, Mullai, Myers, Melanie F., Namjou, Bahram, Ni, Yizhao, Obeng, Aniwaa Owusu, Onofrio, Robert C., Taylor, Casey Overby, Person, Thomas N., Peterson, Josh F., Petukhova, Lynn, Pisieczko, Cassandra J., Pratap, Siddharth, Prows, Cynthia A., Puckelwartz, Megan J., Rahm, Alanna Kulchak, Raj, Ritika, Ralston, James D., Ramaprasan, Arvind, Ramirez, Andrea, Rasmussen, Luke, Rasmussen-Torvik, Laura, Rasouly, Hila Milo, Raychaudhuri, Soumya, Ritchie, Marylyn D., Rives, Catherine, Riza, Beenish, Roden, Dan, Rosenthal, Elisabeth A., Santani, Avni, Schaid, Dan, Scherer, Steven, Scott, Stuart, Scrol, Aaron, Sengupta, Soumitra, Shang, Ning, Sharma, Himanshu, Sharp, Richard R., Singh, Rajbir, Sleiman, Patrick M.A., Slowik, Kara, Smith, Joshua C., Smith, Maureen E., Smoller, Jordan W., Sohn, Sunghwan, Stanaway, Ian B., Starren, Justin, Stroud, Mary, Su, Jessica, Tolwinski, Kasia, Van Driest, Sara L., Vargas, Sean M., Varugheese, Matthew, Veenstra, David, Verbitsky, Miguel, Vicente, Gina, Wagner, Michael, Walker, Kimberly, Walunas, Theresa, Wang, Liwen, Wang, Qiaoyan, Wei, Wei-Qi, Weiss, Scott T., Wiesner, Georgia L., Wells, Quinn, Weng, Chunhua, White, Peter S., Wiley, Ken L., Jr., Williams, Janet L., Williams, Marc S., Wilson, Michael W., Witkowski, Leora, Woods, Laura Allison, Woolf, Betty, Wu, Tsung-Jung, Wynn, Julia, Yang, Yaping, Yi, Victoria, Zhang, Ge, Zhang, Lan, Rehm, Heidi L., and Gibbs, Richard A.
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- 2019
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24. Redefining the Etiologic Landscape of Cerebellar Malformations
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Aldinger, Kimberly A., Timms, Andrew E., Thomson, Zachary, Mirzaa, Ghayda M., Bennett, James T., Rosenberg, Alexander B., Roco, Charles M., Hirano, Matthew, Abidi, Fatima, Haldipur, Parthiv, Cheng, Chi V., Collins, Sarah, Park, Kaylee, Zeiger, Jordan, Overmann, Lynne M., Alkuraya, Fowzan S., Biesecker, Leslie G., Braddock, Stephen R., Cathey, Sara, Cho, Megan T., Chung, Brian H.Y., Everman, David B., Zarate, Yuri A., Jones, Julie R., Schwartz, Charles E., Goldstein, Amy, Hopkin, Robert J., Krantz, Ian D., Ladda, Roger L., Leppig, Kathleen A., McGillivray, Barbara C., Sell, Susan, Wusik, Katherine, Gleeson, Joseph G., Nickerson, Deborah A., Bamshad, Michael J., Gerrelli, Dianne, Lisgo, Steven N., Seelig, Georg, Ishak, Gisele E., Barkovich, A. James, Curry, Cynthia J., Glass, Ian A., Millen, Kathleen J., Doherty, Dan, and Dobyns, William B.
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- 2019
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25. Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway
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Karolak, Justyna A., Vincent, Marie, Deutsch, Gail, Gambin, Tomasz, Cogné, Benjamin, Pichon, Olivier, Vetrini, Francesco, Mefford, Heather C., Dines, Jennifer N., Golden-Grant, Katie, Dipple, Katrina, Freed, Amanda S., Leppig, Kathleen A., Dishop, Megan, Mowat, David, Bennetts, Bruce, Gifford, Andrew J., Weber, Martin A., Lee, Anna F., Boerkoel, Cornelius F., Bartell, Tina M., Ward-Melver, Catherine, Besnard, Thomas, Petit, Florence, Bache, Iben, Tümer, Zeynep, Denis-Musquer, Marie, Joubert, Madeleine, Martinovic, Jelena, Bénéteau, Claire, Molin, Arnaud, Carles, Dominique, André, Gwenaelle, Bieth, Eric, Chassaing, Nicolas, Devisme, Louise, Chalabreysse, Lara, Pasquier, Laurent, Secq, Véronique, Don, Massimiliano, Orsaria, Maria, Missirian, Chantal, Mortreux, Jérémie, Sanlaville, Damien, Pons, Linda, Küry, Sébastien, Bézieau, Stéphane, Liet, Jean-Michel, Joram, Nicolas, Bihouée, Tiphaine, Scott, Daryl A., Brown, Chester W., Scaglia, Fernando, Tsai, Anne Chun-Hui, Grange, Dorothy K., Phillips, John A., 3rd, Pfotenhauer, Jean P., Jhangiani, Shalini N., Gonzaga-Jauregui, Claudia G., Chung, Wendy K., Schauer, Galen M., Lipson, Mark H., Mercer, Catherine L., van Haeringen, Arie, Liu, Qian, Popek, Edwina, Coban Akdemir, Zeynep H., Lupski, James R., Szafranski, Przemyslaw, Isidor, Bertrand, Le Caignec, Cedric, and Stankiewicz, Paweł
- Published
- 2019
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26. Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance.
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Kaiser, Frank J, Ansari, Morad, Braunholz, Diana, Concepción Gil-Rodríguez, María, Decroos, Christophe, Wilde, Jonathan J, Fincher, Christopher T, Kaur, Maninder, Bando, Masashige, Amor, David J, Atwal, Paldeep S, Bahlo, Melanie, Bowman, Christine M, Bradley, Jacquelyn J, Brunner, Han G, Clark, Dinah, Del Campo, Miguel, Di Donato, Nataliya, Diakumis, Peter, Dubbs, Holly, Dyment, David A, Eckhold, Juliane, Ernst, Sarah, Ferreira, Jose C, Francey, Lauren J, Gehlken, Ulrike, Guillén-Navarro, Encarna, Gyftodimou, Yolanda, Hall, Bryan D, Hennekam, Raoul, Hudgins, Louanne, Hullings, Melanie, Hunter, Jennifer M, Yntema, Helger, Innes, A Micheil, Kline, Antonie D, Krumina, Zita, Lee, Hane, Leppig, Kathleen, Lynch, Sally Ann, Mallozzi, Mark B, Mannini, Linda, McKee, Shane, Mehta, Sarju G, Micule, Ieva, Care4Rare Canada Consortium, Mohammed, Shehla, Moran, Ellen, Mortier, Geert R, Moser, Joe-Ann S, Noon, Sarah E, Nozaki, Naohito, Nunes, Luis, Pappas, John G, Penney, Lynette S, Pérez-Aytés, Antonio, Petersen, Michael B, Puisac, Beatriz, Revencu, Nicole, Roeder, Elizabeth, Saitta, Sulagna, Scheuerle, Angela E, Schindeler, Karen L, Siu, Victoria M, Stark, Zornitza, Strom, Samuel P, Thiese, Heidi, Vater, Inga, Willems, Patrick, Williamson, Kathleen, Wilson, Louise C, University of Washington Center for Mendelian Genomics, Hakonarson, Hakon, Quintero-Rivera, Fabiola, Wierzba, Jolanta, Musio, Antonio, Gillessen-Kaesbach, Gabriele, Ramos, Feliciano J, Jackson, Laird G, Shirahige, Katsuhiko, Pié, Juan, Christianson, David W, Krantz, Ian D, Fitzpatrick, David R, and Deardorff, Matthew A
- Subjects
Care4Rare Canada Consortium ,University of Washington Center for Mendelian Genomics ,Humans ,Hypertelorism ,De Lange Syndrome ,Eye Abnormalities ,Histone Deacetylases ,Repressor Proteins ,Cohort Studies ,Sequence Alignment ,Amino Acid Sequence ,Phenotype ,Mutation ,Missense ,Molecular Sequence Data ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Genes ,X-Linked ,Cranial Fontanelles ,Genetics ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Brain Disorders ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Aetiology ,Congenital ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS.
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- 2014
27. Developmental epileptic encephalopathy in DLG4‐related synaptopathy
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Kassabian, Benedetta, primary, Levy, Amanda M., additional, Gardella, Elena, additional, Aledo‐Serrano, Angel, additional, Ananth, Amitha L., additional, Brea‐Fernández, Alejandro J., additional, Caumes, Roseline, additional, Chatron, Nicolas, additional, Dainelli, Alice, additional, De Wachter, Matthias, additional, Denommé‐Pichon, Anne‐Sophie, additional, Dye, Thomas J., additional, Fazzi, Elisa, additional, Felt, Roxanne, additional, Fernández‐Jaén, Alberto, additional, Fernández‐Prieto, Montserrat, additional, Gantz, Emily, additional, Gasperowicz, Piotr, additional, Gil‐Nagel, Antonio, additional, Gómez‐Andrés, David, additional, Greiner, Hansel M., additional, Guerrini, Renzo, additional, Haanpää, Maria K., additional, Helin, Minttu, additional, Hoyer, Juliane, additional, Hurst, Anna C. E., additional, Kallish, Staci, additional, Karkare, Shefali N., additional, Khan, Amjad, additional, Kleinendorst, Lotte, additional, Koch, Johannes, additional, Kothare, Sanjeev V., additional, Koudijs, Suzanna V., additional, Lagae, Lieven, additional, Lakeman, Phillis, additional, Leppig, Kathleen A., additional, Lesca, Gaetan, additional, Lopergolo, Diego, additional, Lusk, Laina, additional, Mackenzie, Alex, additional, Mei, Davide, additional, Møller, Rikke S., additional, Pereira, Elaine M., additional, Platzer, Konrad, additional, Quelin, Chloe, additional, Revah‐Politi, Anya, additional, Rheims, Sylvain, additional, Rodríguez‐Palmero, Agustí, additional, Rossi, Andrea, additional, Santorelli, Filippo, additional, Seinfeld, Syndi, additional, Sell, Erick, additional, Stephenson, Donna, additional, Szczaluba, Krzysztof, additional, Trinka, Eugen, additional, Umair, Muhammad, additional, Van Esch, Hilde, additional, van Haelst, Mieke M., additional, Veenma, Danielle C. M., additional, Weber, Sacha, additional, Weckhuysen, Sarah, additional, Zacher, Pia, additional, Tümer, Zeynep, additional, and Rubboli, Guido, additional
- Published
- 2023
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28. Spliceosome malfunction causes neurodevelopmental disorders with overlapping features
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Li, Dong, primary, Wang, Qin, additional, Bayat, Allan, additional, Battig, Mark R., additional, Zhou, Yijing, additional, Bosch, Daniëlle G.M., additional, van Haaften, Gijs, additional, Granger, Leslie, additional, Petersen, Andrea K., additional, Pérez-Jurado, Luis A., additional, Aznar-Laín, Gemma, additional, Aneja, Anushree, additional, Hancarova, Miroslava, additional, Bendova, Sarka, additional, Schwarz, Martin, additional, Kremlíková Pourová, Radka, additional, Sedlacek, Zdenek, additional, Keena, Beth A., additional, March, Michael E., additional, Hou, Cuiping, additional, O'Connor, Nora, additional, Bhoj, Elizabeth J., additional, Harr, Margaret H., additional, Lemire, Gabrielle, additional, Boycott, Kym M., additional, Towne, Meghan C., additional, Li, Megan, additional, Tarnopolsky, Mark, additional, Brady, Lauren, additional, Parker, Michael J., additional, Faghfoury, Hanna, additional, Parsley, Lea Kristin, additional, Agolini, Emanuele, additional, Dentici, Maria Lisa, additional, Novelli, Antonio, additional, Wright, Meredith S., additional, Palmquist, Rachel, additional, Lai, Khanh, additional, Scala, Marcello, additional, Striano, Pasquale, additional, Iacomino, Michele, additional, Zara, Federico, additional, Cooper, Annina, additional, Maarup, Timothy J., additional, Byler, Melissa, additional, Lebel, Robert Roger, additional, Balci, Tugce B., additional, Louie, Raymond J., additional, Lyons, Michael J., additional, Douglas, Jessica, additional, Nowak, Catherine B., additional, Afenjar, Alexandra, additional, Hoyer, Juliane, additional, Keren, Boris, additional, Maas, Saskia M., additional, Motazacker, Mahdi M., additional, Martinez-Agosto, Julian A., additional, Rabani, Ahna M., additional, McCormick, Elizabeth M., additional, Falk, Marni, additional, Ruggiero, Sarah M., additional, Helbig, Ingo, additional, Møller, Rikke S., additional, Tessarollo, Lino, additional, Tomassoni-Ardori, Francesco, additional, Palko, Mary Ellen, additional, Hsieh, Tzung-Chien, additional, Krawitz, Peter M., additional, Ganapathi, Mythily, additional, Gelb, Bruce D., additional, Jobanputra, Vaidehi, additional, Wilson, Ashley, additional, Greally, John, additional, Jacquemont, Sébastien, additional, Jizi, Khadijé, additional, Ange-Line, Bruel, additional, Quelin, Chloé, additional, Misra, Vinod K., additional, Chick, Erika, additional, Romano, Corrado, additional, Greco, Donatella, additional, Arena, Alessia, additional, Morleo, Manuela, additional, Nigro, Vincenzo, additional, Seyama, Rie, additional, Uchiyama, Yuri, additional, Matsumoto, Naomichi, additional, Taira, Ryoji, additional, Tashiro, Katsuya, additional, Sakai, Yasunari, additional, Yigit, Gökhan, additional, Wollnik, Bernd, additional, Wagner, Michael, additional, Kutsche, Barbara, additional, Hurst, Anna C.E., additional, Thompson, Michelle L., additional, Schmidt, Ryan J., additional, Randolph, Linda M., additional, Spillmann, Rebecca C., additional, Shashi, Vandana, additional, Higginbotham, Edward J., additional, Cordeiro, Dawn, additional, Carnevale, Amanda, additional, Costain, Gregory, additional, Khan, Tayyaba, additional, Funalot, Benoît, additional, Tran Mau-Them, Frederic, additional, Fernandez Garcia Moya, Luis, additional, García-Miñaúr, Sixto, additional, Osmond, Matthew, additional, Chad, Lauren, additional, Quercia, Nada, additional, Carrasco, Diana, additional, Li, Chumei, additional, Sanchez-Valle, Amarilis, additional, Kelley, Meghan, additional, Nizon, Mathilde, additional, Jensson, Brynjar O., additional, Sulem, Patrick, additional, Stefansson, Kari, additional, Gorokhova, Svetlana, additional, Busa, Tiffany, additional, Rio, Marlène, additional, Hadj Abdallah, Hamza, additional, Lesieur-Sebellin, Marion, additional, Amiel, Jeanne, additional, Pingault, Véronique, additional, Mercier, Sandra, additional, Vincent, Marie, additional, Philippe, Christophe, additional, Fatus-Fauconnier, Clemence, additional, Friend, Kathryn, additional, Halligan, Rebecca K., additional, Biswas, Sunita, additional, Rosser, Jane M.R., additional, Shoubridge, Cheryl, additional, Corbett, Mark A., additional, Barnett, Christopher, additional, Gecz, Jozef, additional, Leppig, Kathleen A., additional, Slavotinek, Anne, additional, Marcelis, Carlo, additional, Pfundt, Rolph, additional, de Vries, Bert B.A., additional, van Slegtenhorst, Marjon A., additional, Brooks, Alice S., additional, Cogne, Benjamin, additional, Rambaud, Thomas, additional, Tümer, Zeynep, additional, Zackai, Elaine H., additional, Akizu, Naiara, additional, Song, Yuanquan, additional, and Hakonarson, Hakon, additional
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- 2023
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29. Genetic Heterogeneity and Core Clinical Features of NOG-Related-Symphalangism Spectrum Disorder
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Carlson, Ryan J., Quesnel, Alicia, Wells, Dawson, Brownstein, Zippora, Gilony, Dror, Gulsuner, Suleyman, Leppig, Kathleen A., Avraham, Karen B., King, Mary-Claire, Walsh, Tom, and Rubinstein, Jay
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- 2021
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30. Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants
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Johnston, Jennifer J., van der Smagt, Jasper J., Rosenfeld, Jill A., Pagnamenta, Alistair T., Alswaid, Abdulrahman, Baker, Eva H., Blair, Edward, Borck, Guntram, Brinkmann, Julia, Craigen, William, Dung, Vu Chi, Emrick, Lisa, Everman, David B., van Gassen, Koen L., Gulsuner, Suleyman, Harr, Margaret H., Jain, Mahim, Kuechler, Alma, Leppig, Kathleen A., McDonald-McGinn, Donna M., Can, Ngoc Thi Bich, Peleg, Amir, Roeder, Elizabeth R., Rogers, R.Curtis, Sagi-Dain, Lena, Sapp, Julie C., Schäffer, Alejandro A., Schanze, Denny, Stewart, Helen, Taylor, Jenny C., Verbeek, Nienke E., Walkiewicz, Magdalena A., Zackai, Elaine H., Zweier, Christiane, Zenker, Martin, Lee, Brendan, and Biesecker, Leslie G.
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- 2018
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31. “It would be so much easier”: health system-led genetic risk notification—feasibility and acceptability of cascade screening in an integrated system
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Henrikson, Nora B., Blasi, Paula R., Fullerton, Stephanie M., Grafton, Jane, Leppig, Kathleen A., Jarvik, Gail P., and Larson, Eric B.
- Published
- 2019
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32. Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition
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Vollger, Mitchell R., primary, Korlach, Jonas, additional, Eldred, Kiara C., additional, Swanson, Elliott, additional, Underwood, Jason G., additional, Munson, Katherine M., additional, Cheng, Yong-Han H., additional, Ranchalis, Jane, additional, Mao, Yizi, additional, Blue, Elizabeth E., additional, Schwarze, Ulrike, additional, Saunders, Christopher T., additional, Wenger, Aaron M., additional, Allworth, Aimee, additional, Chanprasert, Sirisak, additional, Duerden, Brittney L., additional, Glass, Ian, additional, Horike-Pyne, Martha, additional, Kim, Michelle, additional, Leppig, Kathleen A., additional, McLaughlin, Ian J., additional, Ogawa, Jessica, additional, Rosenthal, Elisabeth A., additional, Sheppeard, Sam, additional, Sherman, Stephanie M., additional, Strohbehn, Samuel, additional, Yuen, Amy L., additional, Reh, Thomas A., additional, Byers, Peter H., additional, Bamshad, Michael J., additional, Hisama, Fuki M., additional, Jarvik, Gail P., additional, Sancak, Yasemin, additional, Dipple, Katrina M., additional, and Stergachis, Andrew B., additional
- Published
- 2023
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- View/download PDF
33. Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome
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Beysen, Diane, De Jaegere, Sarah, Amor, David, Bouchard, Philippe, Christin‐Maitre, Sophie, Fellous, Marc, Touraine, Philippe, Grix, Arthur W, Hennekam, Raoul, Meire, Françoise, Oyen, Nina, Wilson, Louise C, Barel, Dalit, Clayton‐Smith, Jill, de Ravel, Thomy, Decock, Christian, Delbeke, Patricia, Ensenauer, Regina, Ebinger, Friedrich, Gillessen‐Kaesbach, Gabriele, Hendriks, Yvonne, Kimonis, Virginia, Laframboise, Rachel, Laissue, Paul, Leppig, Kathleen, Leroy, Bart P, Miller, David T, Mowat, David, Neumann, Luitgard, Plomp, Astrid, Van Regemorter, Nicole, Wieczorek, Dagmar, Veitia, Reiner A, De Paepe, Anne, and De Baere, Elfride
- Subjects
Genetics ,Rare Diseases ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Adult ,Amino Acid Sequence ,Blepharophimosis ,Child ,Child ,Preschool ,Codon ,Nonsense ,DNA Mutational Analysis ,Eyelids ,Female ,Forkhead Box Protein L2 ,Forkhead Transcription Factors ,Frameshift Mutation ,Genotype ,Humans ,Infant ,Infant ,Newborn ,Male ,Middle Aged ,Molecular Sequence Data ,Mutation ,Missense ,Pedigree ,Phenotype ,Primary Ovarian Insufficiency ,Sequence Alignment ,Young Adult ,Clinical Sciences ,Genetics & Heredity - Abstract
Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.
- Published
- 2008
34. A web-based personalized risk communication and decision-making tool for women with dense breasts: Design and methods of a randomized controlled trial within an integrated health care system
- Author
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Knerr, Sarah, Wernli, Karen J., Leppig, Kathleen, Ehrlich, Kelly, Graham, Amanda L., Farrell, David, Evans, Chalanda, Luta, George, Schwartz, Marc D., and O’Neill, Suzanne C.
- Published
- 2017
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35. Harmonizing Outcomes for Genomic Medicine: Comparison of eMERGE Outcomes to ClinGen Outcome/Intervention Pairs
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Williams, Janet L., primary, Chung, Wendy K., additional, Fedotov, Alex, additional, Kiryluk, Krzysztof, additional, Weng, Chunhua, additional, Connolly, John J., additional, Harr, Margaret, additional, Hakonarson, Hakon, additional, Leppig, Kathleen A., additional, Larson, Eric B., additional, Jarvik, Gail P., additional, Veenstra, David L., additional, Hoell, Christin, additional, Smith, Maureen E., additional, Holm, Ingrid A., additional, Peterson, Josh F., additional, and Williams, Marc S., additional
- Published
- 2020
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36. Abstract 14663: High Rate of Arrhythmia Diagnoses Following Return of Pathogenic/likely Pathogenic Variants in an Unselected Population
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Davogustto, Giovanni E, Glazer, Andrew, Shaffer, Christian M, Farber-Eger, Eric, Dikilitas, Ozan, Ning, Shang, Pacheco, Jennifer, Mosley, Jonathan, Van Driest, Sara, Wells, Quinn, Rinke, Lauren L, Kalash, Olivia, Wada, Yuko, Bland, Sarah, Yoneda, Zachary T, Kroncke, Brett, Iftikhar, Kullo, Jarvik, Gail P, Gordon, Adam, LARSON, eric B, Manolio, Teri A, Mirshahi, Tooraj, Luo, Jonathan, Schaid, Daniel, Namjou, Bahram, ALSAIED, Tarek, Singh, Rajbir, Singhal, Ashutosh, Ralston, James D, McNally, Elizabeth M, George, Albert, Chung, Wendy, Carrell, David S, Leppig, Kathleen A, Hakonarson, Hakon, Sleiman, Patrick, Sohn, Sunghwan, Glessner, Joseph, Denny, Joshua, Wei, Wei-Qi, Shoemaker, M. Benjamin, and Roden, Dan M
- Published
- 2020
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37. P855: Traceback testing for ovarian cancer: Implementer and participant perspectives*
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Henrikson, Nora, Rahm, Alanna, Blasi, Paula, Leitzel, Tracey, Suwannarat, Pim, Deneal, Adrienne, Leppig, Kathleen, Scrol, Aaron, Canedo, Daniela, and Jonas, M. Cabell
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- 2024
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38. Improving performance of multigene panels for genomic analysis of cancer predisposition
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Shirts, Brian H., Casadei, Silvia, Jacobson, Angela L., Lee, Ming K., Gulsuner, Suleyman, Bennett, Robin L., Miller, Margaret, Hall, Sarah A., Hampel, Heather, Hisama, Fuki M., Naylor, Lorraine V., Goetsch, Cathleen, Leppig, Kathleen, Tait, Jonathan F., Scroggins, Sheena M., Turner, Emily H., Livingston, Robert, Salipante, Stephen J., King, Mary-Claire, Walsh, Tom, and Pritchard, Colin C.
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- 2016
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39. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine
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Amaral, Michelle, Amendola, Laura, Appelbaum, Paul S., Aronson, Samuel J., Arora, Shubhangi, Azzariti, Danielle R., Barsh, Greg S., Bebin, E.M., Biesecker, Barbara B., Biesecker, Leslie G., Biswas, Sawona, Blout, Carrie L., Bowling, Kevin M., Brothers, Kyle B., Brown, Brian L., Burt, Amber A., Byers, Peter H., Caga-anan, Charlisse F., Calikoglu, Muge G., Carlson, Sara J., Chahin, Nizar, Chinnaiyan, Arul M., Christensen, Kurt D., Chung, Wendy, Cirino, Allison L., Clayton, Ellen, Conlin, Laura K., Cooper, Greg M., Crosslin, David R., Davis, James V., Davis, Kelly, Deardorff, Matthew A., Devkota, Batsal, De Vries, Raymond, Diamond, Pamela, Dorschner, Michael O., Dugan, Noreen P., Dukhovny, Dmitry, Dulik, Matthew C., East, Kelly M., Rivera-Munoz, Edgar A., Evans, Barbara, Evans, James P., Everett, Jessica, Exe, Nicole, Fan, Zheng, Feuerman, Lindsay Z., Filipski, Kelly, Finnila, Candice R., Fishler, Kristen, Fullerton, Stephanie M., Ghrundmeier, Bob, Giles, Karen, Gilmore, Marian J., Girnary, Zahra S., Goddard, Katrina, Gonsalves, Steven, Gordon, Adam S., Gornick, Michele C., Grady, William M., Gray, David E., Gray, Stacy W., Green, Robert, Greenwood, Robert S., Gutierrez, Amanda M., Han, Paul, Hart, Ragan, Heagerty, Patrick, Henderson, Gail E., Hensman, Naomi, Hiatt, Susan M., Himes, Patricia, Hindorff, Lucia A., Hisama, Fuki M., Ho, Carolyn Y., Hoffman-Andrews, Lily B., Holm, Ingrid A., Hong, Celine, Horike-Pyne, Martha J., Hull, Sara, Hutter, Carolyn M., Jamal, Seema, Jarvik, Gail P., Jensen, Brian C., Joffe, Steve, Johnston, Jennifer, Karavite, Dean, Kauffman, Tia L., Kaufman, Dave, Kelley, Whitley, Kim, Jerry H., Kirby, Christine, Klein, William, Knoppers, Bartha, Koenig, Barbara A., Kong, Sek Won, Krantz, Ian, Krier, Joel B., Lamb, Neil E., Lambert, Michele P., Le, Lan Q., Lebo, Matthew S., Lee, Alexander, Lee, Kaitlyn B., Lennon, Niall, Leo, Michael C., Leppig, Kathleen A., Lewis, Katie, Lewis, Michelle, Lindeman, Neal I., Lockhart, Nicole, Lonigro, Bob, Lose, Edward J., Lupo, Philip J., Rodriguez, Laura Lyman, Lynch, Frances, Machini, Kalotina, MacRae, Calum, Manolio, Teri A., Marchuk, Daniel S., Martinez, Josue N., Masino, Aaron, McCullough, Laurence, McEwen, Jean, McGuire, Amy, McLaughlin, Heather M., McMullen, Carmit, Mieczkowski, Piotr A., Miller, Jeff, Miller, Victoria A., Mody, Rajen, Mooney, Sean D., Moore, Elizabeth G., Morris, Elissa, Murray, Michael, Muzny, Donna, Myers, Richard M., Ng, David, Nickerson, Deborah A., Oliver, Nelly M., Ou, Jeffrey, Parsons, Will, Patrick, Donald L., Pennington, Jeffrey, Perry, Denise L., Petersen, Gloria, Plon, Sharon, Porter, Katie, Powell, Bradford C., Punj, Sumit, Breitkopf, Carmen Radecki, Raesz-Martinez, Robin A., Raskind, Wendy H., Rehm, Heidi L., Reigar, Dean A., Reiss, Jacob A., Rich, Carla A., Richards, Carolyn Sue, Rini, Christine, Roberts, Scott, Robertson, Peggy D., Robinson, Dan, Robinson, Jill O., Robinson, Marguerite E., Roche, Myra I., Romasko, Edward J., Rosenthal, Elisabeth A., Salama, Joseph, Scarano, Maria I., Schneider, Jennifer, Scollon, Sarah, Seidman, Christine E., Seifert, Bryce A., Sharp, Richard R., Shirts, Brian H., Sholl, Lynette M., Siddiqui, Javed, Silverman, Elian, Simmons, Shirley, Simons, Janae V., Skinner, Debra, Spinner, Nancy B., Stoffel, Elena, Strande, Natasha T., Sunyaev, Shamil, Sybert, Virginia P., Taber, Jennifer, Tabor, Holly K., Tarczy-Hornoch, Peter, Taylor, Deanne M., Tilley, Christian R., Tomlinson, Ashley, Trinidad, Susan, Tsai, Ellen, Ubel, Peter, Van Allen, Eliezer M., Vassy, Jason L., Vats, Pankaj, Veenstra, David L., Vetter, Victoria L., Vries, Raymond D., Wagle, Nikhil, Walser, Sarah A., Walsh, Rebecca C., Weck, Karen, Werner-Lin, Allison, Whittle, Jana, Wilfond, Ben, Wilhelmsen, Kirk C., Wolf, Susan M., Wynn, Julia, Yang, Yaping, Young, Carol, Yu, Joon-Ho, Zikmund-Fisher, Brian J., Green, Robert C., Goddard, Katrina A.B., Amendola, Laura M., Berg, Jonathan S., Bernhardt, Barbara A., Burke, Wylie, Chung, Wendy K., Clayton, Ellen W., Cooper, Gregory M., East, Kelly, Garraway, Levi A., Garrett, Jeremy R., Lewis, Michelle Huckaby, Janne, Pasi A., Joffe, Steven, Kaufman, David, Knoppers, Bartha M., Krantz, Ian D., Parsons, Donald W., Petersen, Gloria M., Plon, Sharon E., Roberts, J. Scott, Salama, Joseph S., Shirts, Brian, Wilfond, Benjamin S., and Wilhelmsen, Kirk
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- 2016
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40. Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome
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Pujol-Giménez, Jonai, Mirzaa, Ghayda, Blue, Elizabeth E, Albano, Giuseppe, Miller, Danny E, Allworth, Aimee, Bennett, James T, Byers, Peter H, Chanprasert, Sirisak, Chen, Jingheng, Doherty, Daniel, Folta, Andrew B, Gillentine, Madelyn A, Glass, Ian, Hing, Anne, Horike-Pyne, Martha, Leppig, Kathleen A, Parhin, Azma, Ranchalis, Jane, Raskind, Wendy H, Rosenthal, Elisabeth A, Schwarze, Ulrike, Sheppeard, Sam, Strohbehn, Samuel, Sybert, Virginia P, Timms, Andrew, Wener, Mark, Bamshad, Michael J, Hisama, Fuki M, Jarvik, Gail P, Dipple, Katrina M, Hediger, Matthias A., and Stergachis, Andrew B
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610 Medicine & health - Abstract
SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine.
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- 2023
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41. A phenome-wide association study to discover pleiotropic effects of PCSK9, APOB, and LDLR
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Safarova, Maya S., Satterfield, Benjamin A., Fan, Xiao, Austin, Erin E., Ye, Zhan, Bastarache, Lisa, Zheng, Neil, Ritchie, Marylyn D., Borthwick, Kenneth M., Williams, Marc S., Larson, Eric B., Scrol, Aaron, Jarvik, Gail P., Crosslin, David R., Leppig, Kathleen, Rasmussen-Torvik, Laura J., Pendergrass, Sarah A., Sturm, Amy C., Namjou, Bahram, Shah, Amy Sanghavi, Carroll, Robert J., Chung, Wendy K., Wei, Wei-Qi, Feng, QiPing, Stein, C. Michael, Roden, Dan M., Manolio, Teri A., Schaid, Daniel J., Denny, Joshua C., Hebbring, Scott J., de Andrade, Mariza, and Kullo, Iftikhar J.
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- 2019
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42. Returning integrated genomic risk and clinical recommendations: The eMERGE study
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Linder, Jodell E., primary, Allworth, Aimee, additional, Bland, Sarah T., additional, Caraballo, Pedro J., additional, Chisholm, Rex L., additional, Clayton, Ellen Wright, additional, Crosslin, David R., additional, Dikilitas, Ozan, additional, DiVietro, Alanna, additional, Esplin, Edward D., additional, Forman, Sophie, additional, Freimuth, Robert R., additional, Gordon, Adam S., additional, Green, Richard, additional, Harden, Maegan V., additional, Holm, Ingrid A., additional, Jarvik, Gail P., additional, Karlson, Elizabeth W., additional, Labrecque, Sofia, additional, Lennon, Niall J., additional, Limdi, Nita A., additional, Mittendorf, Kathleen F., additional, Murphy, Shawn N., additional, Orlando, Lori, additional, Prows, Cynthia A., additional, Rasmussen, Luke V., additional, Rasmussen-Torvik, Laura, additional, Rowley, Robb, additional, Sawicki, Konrad Teodor, additional, Schmidlen, Tara, additional, Terek, Shannon, additional, Veenstra, David, additional, Velez Edwards, Digna R., additional, Absher, Devin, additional, Abul-Husn, Noura S., additional, Alsip, Jorge, additional, Bangash, Hana, additional, Beasley, Mark, additional, Below, Jennifer E., additional, Berner, Eta S., additional, Booth, James, additional, Chung, Wendy K., additional, Cimino, James J., additional, Connolly, John, additional, Davis, Patrick, additional, Devine, Beth, additional, Fullerton, Stephanie M., additional, Guiducci, Candace, additional, Habrat, Melissa L., additional, Hain, Heather, additional, Hakonarson, Hakon, additional, Harr, Margaret, additional, Haverfield, Eden, additional, Hernandez, Valentina, additional, Hoell, Christin, additional, Horike-Pyne, Martha, additional, Hripcsak, George, additional, Irvin, Marguerite R., additional, Kachulis, Christopher, additional, Karavite, Dean, additional, Kenny, Eimear E., additional, Khan, Atlas, additional, Kiryluk, Krzysztof, additional, Korf, Bruce, additional, Kottyan, Leah, additional, Kullo, Iftikhar J., additional, Larkin, Katie, additional, Liu, Cong, additional, Malolepsza, Edyta, additional, Manolio, Teri A., additional, May, Thomas, additional, McNally, Elizabeth M., additional, Mentch, Frank, additional, Miller, Alexandra, additional, Mooney, Sean D., additional, Murali, Priyanka, additional, Mutai, Brenda, additional, Muthu, Naveen, additional, Namjou, Bahram, additional, Perez, Emma F., additional, Puckelwartz, Megan J., additional, Rakhra-Burris, Tejinder, additional, Roden, Dan M., additional, Rosenthal, Elisabeth A., additional, Saadatagah, Seyedmohammad, additional, Sabatello, Maya, additional, Schaid, Dan J., additional, Schultz, Baergen, additional, Seabolt, Lynn, additional, Shaibi, Gabriel Q., additional, Sharp, Richard R., additional, Shirts, Brian, additional, Smith, Maureen E., additional, Smoller, Jordan W., additional, Sterling, Rene, additional, Suckiel, Sabrina A., additional, Thayer, Jeritt, additional, Tiwari, Hemant K., additional, Trinidad, Susan B., additional, Walunas, Theresa, additional, Wei, Wei-Qi, additional, Wells, Quinn S., additional, Weng, Chunhua, additional, Wiesner, Georgia L., additional, Wiley, Ken, additional, Peterson, Josh F., additional, Gordon, Adam, additional, Sobowale, Agboade, additional, Patel, Akshar, additional, Strong, Alanna, additional, Sherafati, Alborz, additional, Sherfati, Alborz, additional, Bick, Alex, additional, Chandel, Alka, additional, Rosenthal, Alyssa, additional, Khera, Amit, additional, Kontorovich, Amy, additional, Beck, Andrew, additional, Beck, Andy, additional, Espinoza, Angelica, additional, Lewis, Anna, additional, Prince, Anya, additional, Iverson, Ayuko, additional, Khales, Bahram Namjou, additional, Benoit, Barbara, additional, Hernan, Becca, additional, Kallman, Ben, additional, Kerman, Ben, additional, Shoemaker, Ben, additional, Satterfield, Benjamin, additional, Etheridge, Bethany, additional, Goff, Blake, additional, Freimuth, Bob, additional, Grundmeier, Bob, additional, Collier, Brenae, additional, Harnett, Brett, additional, Chang, Brian, additional, Piening, Brian, additional, Davis, Brittney, additional, Patterson, Candace, additional, Demetriou, Carmen, additional, Ta, Casey, additional, Hammack, Catherine, additional, Nelson, Catrina, additional, Gascoigne, Caytie, additional, Dorn, Chad, additional, Moretz, Chad, additional, Kachulis, Chris, additional, Hoell, Christie, additional, Cowles, Christine, additional, Lange, Christoph, additional, Prows, Cindy, additional, Brokamp, Cole, additional, Scherr, Courtney, additional, Gonzalez, Crystal, additional, Ramirez, Cynthia, additional, Shimbo, Daichi, additional, Roden, Dan, additional, Schaid, Daniel, additional, Kaufman, Dave, additional, Crosslin, David, additional, Kochan, David, additional, Singh, Davinder, additional, Abrams, Debbie, additional, Edwards, Digna Velez, additional, Morales, Eduardo, additional, Esplin, Edward, additional, Alipour, Ehsan, additional, Kenny, Eimear, additional, Rosenthal, Elisabeth, additional, Duvall, Eliza, additional, McNally, Elizabeth, additional, Bhoj, Elizabeth, additional, Cohn, Elizabeth, additional, Hibler, Elizabeth, additional, Karlson, Elizabeth, additional, Clayton, Ellen, additional, Chesnut, Emily, additional, DeFranco, Emily, additional, Gallagher, Emily, additional, Soper, Emily, additional, Perez, Emma, additional, Cash, Erin, additional, Berner, Eta, additional, Wang, Fei, additional, Wehbe, Firas, additional, Ricci, Francisco, additional, Shaibi, Gabriel, additional, Jarvik, Gail, additional, Hahn, George, additional, Wiesner, Georgia, additional, Belbin, Gillian, additional, Davogustto, Gio, additional, Nadkarni, Girish, additional, Qiu, Haijun, additional, Beasley, Hannah, additional, Liu, Hao, additional, Aungst, Heide, additional, Tiwari, Hemant, additional, Duckham, Hillary, additional, Thomas, Hope, additional, Kullo, Iftikhar, additional, Holm, Ingrid, additional, Allen, Isabelle, additional, Ionita-Laza, Iuliana, additional, Hellwege, Jacklyn, additional, Petrzelka, Jacob, additional, Odgis, Jacqueline, additional, Narula, Jahnavi, additional, Petrzelka, Jake, additional, Patel, Jalpa, additional, Cimino, James, additional, Meigs, James, additional, Snyder, James, additional, Olson, Janet, additional, Zahner, Janet, additional, Pennington, Jeff, additional, Pacheco, Jen, additional, Pacheco, Jennifer Allen, additional, Morse, Jennifer, additional, Corsmo, Jeremy, additional, Cimino, Jim, additional, Chen, Jingheng, additional, Fournier, Jocelyn, additional, Jackson, Jodell, additional, Glessner, Joe, additional, Pacyna, Joel, additional, Smith, Johanna, additional, Lynch, John, additional, Shelley, John, additional, Mosley, Jonathan, additional, Nestor, Jordan, additional, Smoller, Jordan, additional, Kannry, Joseph, additional, Sutton, Joseph, additional, Peterson, Josh, additional, Smith, Joshua, additional, Galasso, Julia, additional, Smith, Julia, additional, Wynn, Julia, additional, Gundelach, Justin, additional, Starren, Justin, additional, Choi, Karmel, additional, Mittendorf, Kate, additional, Anderson, Katherine, additional, Bonini, Katherine, additional, Leppig, Kathleen, additional, Muenzen, Kathleen, additional, Stuttgen, Kelsey, additional, Nguyen, Kenny, additional, Dufendach, Kevin, additional, Atkins, Kiley, additional, Sawicki, Konrad, additional, Norland, Kristjan, additional, Beskow, Laura, additional, Hsu, Li, additional, Tian, Lifeng, additional, Mahanta, Lisa, additional, Martin, Lisa, additional, Wang, Lisa, additional, Gomez, Lizbeth, additional, Thompson, Lorenzo, additional, Richter, Lucas, additional, Rasmussen, Luke, additional, Petukhova, Lynn, additional, O’Brien, Madison, additional, Harden, Maegan, additional, Fullerton, Malia, additional, Guindo, Marta, additional, Horike, Martha, additional, Abdalla, Marwah, additional, Hamed, Marwan, additional, Terry, Mary Beth, additional, Maradik, Mary, additional, Wyatt, Matt, additional, Davis, Matthew, additional, Lebo, Matthew, additional, Smith, Maureen, additional, Rosario, Maya del, additional, Behr, Meckenzie, additional, Roy-Puckelwartz, Meg, additional, Habrat, Mel, additional, Myers, Melanie, additional, Yetisgen, Meliha, additional, Iris, Merve, additional, DaSilva, Michael, additional, Preuss, Michael, additional, McGowan, Michelle, additional, Shi, Mingjian, additional, Perera, Minoli, additional, Thomas, Minta, additional, Elkind, Mitch, additional, Abbass, Mohammad, additional, Saadatagah, Mohammad, additional, Hess, Molly, additional, Maradik, Molly, additional, Vaitinadin, Nataraja “RJ”, additional, Vaitinadin, Nataraja, additional, Netherly, Neil, additional, Lennon, Niall, additional, Shang, Ning, additional, Limdi, Nita, additional, Forrest, Noah, additional, Romero, Noheli, additional, Robinson, Nora, additional, Abul-Husn, Noura, additional, Elsekaily, Omar, additional, Kovatch, Patricia, additional, Appelbaum, Paul, additional, Francaviglia, Paul, additional, O’Reilly, Paul, additional, Chandler, Paulette, additional, Caraballo, Pedro, additional, Tarczy-Hornoch, Peter, additional, Shum, Pierre, additional, Marathe, Priya, additional, Feng, Qiping, additional, Wells, Quinn, additional, Atchley, Rachel, additional, Narla, Radhika, additional, Barton, Rene, additional, Chisholm, Rex, additional, Sharp, Richard, additional, Peters, Riki, additional, Kukafka, Rita, additional, Freimuth, Robert, additional, Green, Robert, additional, Winter, Robert, additional, Mueller, Roger, additional, Loos, Ruth, additional, Irvin, Ryan, additional, Suckiel, Sabrina, additional, Hussain, Sajjad, additional, Sharba, Samer, additional, Aronson, Sandy, additional, Jones, Sarah, additional, Knerr, Sarah, additional, Nigbur, Scott, additional, Weiss, Scott, additional, Mooney, Sean, additional, Aufox, Sharon, additional, Nirenberg, Sharon, additional, Murphy, Shawn, additional, O’Byrne, Sheila, additional, Wang (Sam) Choi, Shing, additional, Aguilar, Sienna, additional, Bland, S.T., additional, Rodrigues, Stefanie, additional, Ledbetter, Stephanie, additional, Rutledge, Stephanie, additional, Booth, Stuart James, additional, Xian, Su, additional, Trinidad, Susan Brown, additional, Bakken, Suzanne, additional, Manolio, Teri, additional, Mersha, Tesfaye, additional, Chandereng, Thevaa, additional, Ge, Tian, additional, Edwards, Todd, additional, Kaszemacher, Tom, additional, Willis, Valerie, additional, Desai, Vemi, additional, Desai, Vimi, additional, Lorenzi, Virginia, additional, Gainer, Vivian, additional, Chung, Wendy, additional, Su, Wu-Chen, additional, Chang, Xiao, additional, Zhao, Yiqing, additional, Luo, Yuan, additional, and Shen, Yufeng, additional
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- 2023
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43. Genetic Predictors of Blood Pressure Traits are Associated with Preeclampsia
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Jasper, Elizabeth A., primary, Hellwege, Jacklyn N., additional, Breeyear, Joseph H., additional, Xiao, Brenda, additional, Jarvik, Gail P., additional, Stanaway, Ian B., additional, Leppig, Kathleen A., additional, Chittoor, Geetha, additional, Hayes, M. Geoffrey, additional, Dikilitas, Ozan, additional, Kullo, Iftikhar J., additional, Holm, Ingrid A., additional, Verma, Shefali Setia, additional, Edwards, Todd L., additional, and Velez Edwards, Digna R., additional
- Published
- 2023
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44. Full-length isoform sequencing for resolving the molecular basis of Charcot-Marie-Tooth 2A
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Stergachis, Andrew B., primary, Blue, Elizabeth E., additional, Gillentine, Madelyn A, additional, Wang, Lee-kai, additional, Schwarze, Ulrike, additional, Sedeno Cortes, Adriana, additional, Ranchalis, Jane, additional, Allworth, Aimee, additional, Bland, Austin E., additional, Chanprasert, Sirisak, additional, Chen, Jingheng, additional, Doherty, Daniel, additional, Folta, Andrew B., additional, Glass, Ian, additional, Horike-Pyne, Martha, additional, Huang, Alden Y., additional, Khan, Alyna T., additional, Leppig, Kathleen A., additional, Miller, Danny E., additional, Mirzaa, Ghayda, additional, Parhin, Azma, additional, Raskind, Wendy, additional, Rosenthal, Elisabeth A., additional, Sheppeard, Sam, additional, Strohbehn, Samuel, additional, Sybert, Virginia P., additional, Tran, Thao T., additional, Wener, Mark, additional, Byers, Peter H., additional, Nelson, Stanley F., additional, Bamshad, Michael J., additional, Dipple, Katrina M., additional, Jarvik, Gail P., additional, Hoppins, Suzanne, additional, and Hisama, Fuki M., additional
- Published
- 2023
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45. Full-length isoform sequencing for resolving the molecular basis of Charcot-Marie-Tooth 2A
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Stergachis, Andrew B., Blue, Elizabeth E., Gillentine, Madelyn A, Wang, Lee-kai, Schwarze, Ulrike, Cortés, Adriana Sedeño, Ranchalis, Jane, Allworth, Aimee, Bland, Austin E., Chanprasert, Sirisak, Chen, Jingheng, Doherty, Daniel, Folta, Andrew B., Glass, Ian, Horike-Pyne, Martha, Huang, Alden Y., Khan, Alyna T., Leppig, Kathleen A., Miller, Danny E., Mirzaa, Ghayda, Parhin, Azma, Raskind, Wendy, Rosenthal, Elisabeth A., Sheppeard, Sam, Strohbehn, Samuel, Sybert, Virginia P., Tran, Thao T., Wener, Mark, Byers, Peter H., Nelson, Stanley F., Bamshad, Michael J., Dipple, Katrina M., Jarvik, Gail P., Hoppins, Suzanne, and Hisama, Fuki M.
- Subjects
Article - Abstract
ObjectivesTranscript sequencing of patient derived samples has been shown to improve the diagnostic yield for solving cases of likely Mendelian disorders, yet the added benefit of full-length long-read transcript sequencing is largely unexplored.MethodsWe applied short-read and full-length isoform cDNA sequencing and mitochondrial functional studies to a patient-derived fibroblast cell line from an individual with neuropathy that previously lacked a molecular diagnosis.ResultsWe identified an intronic homozygousMFN2c.600-31T>G variant that disrupts a branch point critical for intron 6 spicing. Full-length long-read isoform cDNA sequencing after treatment with a nonsense-mediated mRNA decay (NMD) inhibitor revealed that this variant creates five distinct altered splicing transcripts. All five altered splicing transcripts have disrupted open reading frames and are subject to NMD. Furthermore, a patient-derived fibroblast line demonstrated abnormal lipid droplet formation, consistent with MFN2 dysfunction. Although correctly spliced full-lengthMFN2transcripts are still produced, this branch point variant results in deficient MFN2 protein levels and autosomal recessive Charcot-Marie-Tooth disease, axonal, type 2A (CMT2A).DiscussionThis case highlights the utility of full-length isoform sequencing for characterizing the molecular mechanism of undiagnosed rare diseases and expands our understanding of the genetic basis for CMT2A.
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- 2023
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46. A Report on Ten Asia Pacific Countries on Current Status and Future Directions of the Genetic Counseling Profession: The Establishment of the Professional Society of Genetic Counselors in Asia
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Laurino, Mercy Y., Leppig, Kathleen A., Abad, Peter James, Cham, Breana, Chu, Yoyo Wing Yiu, Kejriwal, Saahil, Lee, Juliana M. H., Sternen, Darci L., Thompson, Jennifer K., Burgess, Matthew J., Chien, Shu, Elackatt, Niby, Lim, Jiin Ying, Sura, Thanyachai, Faradz, Sultana, Padilla, Carmencita, Paz, Eva Cutiongco de-la, Nauphar, Donny, Nguyen, Khanh Ngoc, Zayts, Olya, Vu, Dung Chi, and Thong, Meow-Keong
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- 2017
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47. Identifying opportunities for collaboration and growth of genetic counseling services in the Asia Region
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Laurino, Mercy Y., Sternen, Darci L., Thompson, Jennifer K., and Leppig, Kathleen A.
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- 2017
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48. P390: Health system direct contact of relatives for cascade testing: Reach and initial acceptability in a prospective intervention study*
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Henrikson, Nora, primary, Zepp, Jamilyn, additional, Blasi, Paula, additional, Anderson, Melissa, additional, Scrol, Aaron, additional, Grafton, Jane, additional, Ewing, John, additional, Ralston, James, additional, Fullerton, Stephanie, additional, and Leppig, Kathleen, additional
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- 2023
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49. P228: Sporadic and inherited genetic variants causing a blended phenotype in a patient with Kabuki syndrome and Loeys-Dietz syndrome, type 3
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Pierce, Corina, primary, Beebe, Kathryn, additional, Balton, Elsa, additional, Thiese, Heidi, additional, and Leppig, Kathleen, additional
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- 2023
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50. P068: Feasibility and initial participation in traceback cascade screening programs for ovarian cancer implemented at three integrated health systems
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Leitzel, Tracey, primary, Rahm, Alanna Kulchak, additional, Patel, Saumya, additional, Schwiter, Rachel, additional, Lewis, Meredith, additional, Hu, Yirui, additional, Jonas, M. Cabell, additional, Suwannarat, Pim, additional, Deneal, Adrienne, additional, Basra, Sundeep, additional, Brown, Jennifer, additional, Khieu, Estella, additional, Balton, Elsa, additional, Ramaprasan, Arvind, additional, Leppig, Kathleen, additional, Scrol, Aaron, additional, and Henrikson, Nora, additional
- Published
- 2023
- Full Text
- View/download PDF
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