Author: "Chao, Katherine R." - Searchworks@Jio Institute Digital Library Search Results

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136 results on '"Chao, Katherine R."'

1. Differential inclusion of NEB exons 143 and 144 provides insight into NEB-related myopathy variant interpretation and disease manifestation

Author: Silverstein, Sarah, Orbach, Rotem, Syeda, Safoora, Foley, A. Reghan, Gorokhova, Svetlana, Meilleur, Katherine G., Leach, Meganne E., Uapinyoying, Prech, Chao, Katherine R., Donkervoort, Sandra, and Bönnemann, Carsten G.
Published: 2025
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2. Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease

Author: Lemire, Gabrielle, Sanchis-Juan, Alba, Russell, Kathryn, Baxter, Samantha, Chao, Katherine R., Singer-Berk, Moriel, Groopman, Emily, Wong, Isaac, England, Eleina, Goodrich, Julia, Pais, Lynn, Austin-Tse, Christina, DiTroia, Stephanie, O’Heir, Emily, Ganesh, Vijay S., Wojcik, Monica H., Evangelista, Emily, Snow, Hana, Osei-Owusu, Ikeoluwa, Fu, Jack, Singh, Mugdha, Mostovoy, Yulia, Huang, Steve, Garimella, Kiran, Kirkham, Samantha L., Neil, Jennifer E., Shao, Diane D., Walsh, Christopher A., Argilli, Emanuela, Le, Carolyn, Sherr, Elliott H., Gleeson, Joseph G., Shril, Shirlee, Schneider, Ronen, Hildebrandt, Friedhelm, Sankaran, Vijay G., Madden, Jill A., Genetti, Casie A., Beggs, Alan H., Agrawal, Pankaj B., Bujakowska, Kinga M., Place, Emily, Pierce, Eric A., Donkervoort, Sandra, Bönnemann, Carsten G., Gallacher, Lyndon, Stark, Zornitza, Tan, Tiong Yang, White, Susan M., Töpf, Ana, Straub, Volker, Fleming, Mark D., Pollak, Martin R., Õunap, Katrin, Pajusalu, Sander, Donald, Kirsten A., Bruwer, Zandre, Ravenscroft, Gianina, Laing, Nigel G., MacArthur, Daniel G., Rehm, Heidi L., Talkowski, Michael E., Brand, Harrison, and O’Donnell-Luria, Anne
Published: 2024
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3. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections

Author: Borras, Silvia, Clark, Caroline, Dean, John, Miedzybrodzka, Zosia, Ross, Alison, Tennant, Stephen, Dabir, Tabib, Donnelly, Deirdre, Humphreys, Mervyn, Magee, Alex, McConnell, Vivienne, McKee, Shane, McNerlan, Susan, Morrison, Patrick J., Rea, Gillian, Stewart, Fiona, Cole, Trevor, Cooper, Nicola, Cooper-Charles, Lisa, Cox, Helen, Islam, Lily, Jarvis, Joanna, Keelagher, Rebecca, Lim, Derek, McMullan, Dominic, Morton, Jenny, Naik, Swati, O’Driscoll, Mary, Ong, Kai-Ren, Osio, Deborah, Ragge, Nicola, Turton, Sarah, Vogt, Julie, Williams, Denise, Bodek, Simon, Donaldson, Alan, Hills, Alison, Low, Karen, Newbury-Ecob, Ruth, Norman, Andrew M., Roberts, Eileen, Scurr, Ingrid, Smithson, Sarah, Tooley, Madeleine, Abbs, Steve, Armstrong, Ruth, Dunn, Carolyn, Holden, Simon, Park, Soo-Mi, Paterson, Joan, Raymond, Lucy, Reid, Evan, Sandford, Richard, Simonic, Ingrid, Tischkowitz, Marc, Woods, Geoff, Bradley, Lisa, Comerford, Joanne, Green, Andrew, Lynch, Sally, McQuaid, Shirley, Mullaney, Brendan, Berg, Jonathan, Goudie, David, Mavrak, Eleni, McLean, Joanne, McWilliam, Catherine, Reavey, Eleanor, Azam, Tara, Cleary, Elaine, Jackson, Andrew, Lam, Wayne, Lampe, Anne, Moore, David, Porteous, Mary, Baple, Emma, Baptista, Júlia, Brewer, Carole, Castle, Bruce, Kivuva, Emma, Owens, Martina, Rankin, Julia, Shaw-Smith, Charles, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Bradley, Therese, Davidson, Rosemarie, Gardiner, Carol, Joss, Shelagh, Kinning, Esther, Longman, Cheryl, McGowan, Ruth, Murday, Victoria, Pilz, Daniela, Tobias, Edward, Whiteford, Margo, Williams, Nicola, Barnicoat, Angela, Clement, Emma, Faravelli, Francesca, Hurst, Jane, Jenkins, Lucy, Jones, Wendy, Ajith Kumar, V.K., Lees, Melissa, Loughlin, Sam, Male, Alison, Morrogh, Deborah, Rosser, Elisabeth, Scott, Richard, Wilson, Louise, Beleza, Ana, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Irving, Melita, Izatt, Louise, Josifova, Dragana, Mohammed, Shehla, Molenda, Aneta, Robert, Leema, Roworth, Wendy, Ruddy, Deborah, Ryten, Mina, Yau, Shu, Bennett, Christopher, Blyth, Moira, Campbell, Jennifer, Coates, Andrea, Dobbie, Angus, Hewitt, Sarah, Hobson, Emma, Jackson, Eilidh, Jewell, Rosalyn, Kraus, Alison, Prescott, Katrina, Sheridan, Eamonn, Thomson, Jenny, Bradshaw, Kirsty, Dixit, Abhijit, Eason, Jacqueline, Haines, Rebecca, Harrison, Rachel, Mutch, Stacey, Sarkar, Ajoy, Searle, Claire, Shannon, Nora, Sharif, Abid, Suri, Mohnish, Vasudevan, Pradeep, Canham, Natalie, Ellis, Ian, Greenhalgh, Lynn, Howard, Emma, Stinton, Victoria, Swale, Andrew, Weber, Astrid, Banka, Siddharth, Breen, Catherine, Briggs, Tracy, Burkitt-Wright, Emma, Chandler, Kate, Clayton-Smith, Jill, Donnai, Dian, Douzgou, Sofia, Gaunt, Lorraine, Jones, Elizabeth, Kerr, Bronwyn, Langley, Claire, Metcalfe, Kay, Smith, Audrey, Wright, Ronnie, Bourn, David, Burn, John, Fisher, Richard, Hellens, Steve, Henderson, Alex, Montgomery, Tara, Splitt, Miranda, Straub, Volker, Wright, Michael, Zwolinski, Simon, Allen, Zoe, Bernhard, Birgitta, Brady, Angela, Brooks, Claire, Busby, Louise, Clowes, Virginia, Ghali, Neeti, Holder, Susan, Ibitoye, Rita, Wakeling, Emma, Blair, Edward, Carmichael, Jenny, Cilliers, Deirdre, Clasper, Susan, Gibbons, Richard, Kini, Usha, Lester, Tracy, Nemeth, Andrea, Poulton, Joanna, Price, Sue, Shears, Debbie, Stewart, Helen, Wilkie, Andrew, Albaba, Shadi, Baker, Duncan, Balasubramanian, Meena, Johnson, Diana, Parker, Michael, Quarrell, Oliver, Stewart, Alison, Willoughby, Josh, Crosby, Charlene, Elmslie, Frances, Homfray, Tessa, Jin, Huilin, Lahiri, Nayana, Mansour, Sahar, Marks, Karen, McEntagart, Meriel, Saggar, Anand, Tatton-Brown, Kate, Butler, Rachel, Clarke, Angus, Corrin, Sian, Fry, Andrew, Kamath, Arveen, McCann, Emma, Mugalaasi, Hood, Pottinger, Caroline, Procter, Annie, Sampson, Julian, Sansbury, Francis, Varghese, Vinod, Baralle, Diana, Callaway, Alison, Cassidy, Emma J., Daniels, Stacey, Douglas, Andrew, Foulds, Nicola, Hunt, David, Kharbanda, Mira, Lachlan, Katherine, Mercer, Catherine, Side, Lucy, Temple, I. Karen, Wellesley, Diana, Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., FurióTarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., MaleadyCrowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Acosta, Maria T., Adam, Margaret, Adams, David R., Agrawal, Pankaj B., Alejandro, Mercedes E., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Peter Chang, Ta Chen, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G., Deardorff, Matthew, Dell'Angelica, Esteban C., Dhar, Shweta U., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Douine, Emilie D., Draper, David D., Duncan, Laura, Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Estwick, Tyra, Falk, Marni, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Findley, Laurie C., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Fresard, Laure, Gahl, William A., Glass, Ian, Godfrey, Rena A., Golden-Grant, Katie, Goldman, Alica M., Goldstein, David B., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Gutierrez, Irma, Hahn, Sihoun, Hamid, Rizwan, Hanchard, Neil A., Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Johnston, Jean M., Karaviti, Lefkothea, Kelley, Emily G., Kennedy, Jennifer, Kiley, Dana, Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Korrick, Susan, Koziura, Mary, Krier, Joel B., Lalani, Seema R., Lam, Byron, Lam, Christina, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Mak, Bryan, Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Markello, Thomas C., Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McCormack, Colleen E., McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nakano-Okuno, Mariko, Nath, Avi, Nelson, Stan F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Papp, Jeanette C., Parker, Neil H., Phillips, John A., Posey, Jennifer E., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raskind, Wendy, Raja, Archana N., Rao, Deepak A., Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Scott, C. Ron, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Sharma, Prashant, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solem, Emily, Solnica-Krezel, Lilianna, Stoler, Joan M., Stong, Nicholas, Sullivan, Jennifer A., Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tamburro, Cecelia P., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Tucker, Brianna M., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Wallace, Stephanie, Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-Kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Wener, Mark, Wenger, Tara, Perry, Katherine Wesseling, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Woods, Jeremy D., Yamamoto, Shinya, Yang, John, Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Jeffries, Lauren, Mis, Emily K., McWalter, Kirsty, Donkervoort, Sandra, Brodsky, Nina N., Carpier, Jean-Marie, Ji, Weizhen, Ionita, Cristian, Roy, Bhaskar, Morrow, Jon S., Darbinyan, Armine, Iyer, Krishna, Aul, Ritu B., Chao, Katherine R., Cobbold, Laura, Cohen, Stacey, Custodio, Helena M., Drummond-Borg, Margaret, Finanger, Erika, Hainline, Bryan E., Helbig, Ingo, Hewson, Stacy, Hu, Ying, Jackson, Adam, Konstantino, Monica, Leach, Meganne E., McCormick, David, Nelson, Stanley, Nguyen, Joanne, Nugent, Kimberly, Ortega, Lucy, Goodkin, Howard P., Roeder, Elizabeth, Roy, Sani, Sapp, Katie, Saade, Dimah, Sisodiya, Sanjay M., Stals, Karen, Towner, Shelley, Wilson, William, Khokha, Mustafa K., Bönnemann, Carsten G., Lucas, Carrie L., and Lakhani, Saquib A.
Published: 2024
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4. Genome Sequencing for Diagnosing Rare Diseases

Author: Wojcik, Monica H., primary, Lemire, Gabrielle, additional, Berger, Eva, additional, Zaki, Maha S., additional, Wissmann, Mariel, additional, Win, Wathone, additional, White, Susan M., additional, Weisburd, Ben, additional, Wieczorek, Dagmar, additional, Waddell, Leigh B., additional, Verboon, Jeffrey M., additional, VanNoy, Grace E., additional, Töpf, Ana, additional, Tan, Tiong Yang, additional, Syrbe, Steffen, additional, Strehlow, Vincent, additional, Straub, Volker, additional, Stenton, Sarah L., additional, Snow, Hana, additional, Singer-Berk, Moriel, additional, Silver, Josh, additional, Shril, Shirlee, additional, Seaby, Eleanor G., additional, Schneider, Ronen, additional, Sankaran, Vijay G., additional, Sanchis-Juan, Alba, additional, Russell, Kathryn A., additional, Reinson, Karit, additional, Ravenscroft, Gianina, additional, Radtke, Maximilian, additional, Popp, Denny, additional, Polster, Tilman, additional, Platzer, Konrad, additional, Pierce, Eric A., additional, Place, Emily M., additional, Pajusalu, Sander, additional, Pais, Lynn, additional, Õunap, Katrin, additional, Osei-Owusu, Ikeoluwa, additional, Opperman, Henry, additional, Okur, Volkan, additional, Oja, Kaisa Teele, additional, O’Leary, Melanie, additional, O’Heir, Emily, additional, Morel, Chantal F., additional, Merkenschlager, Andreas, additional, Marchant, Rhett G., additional, Mangilog, Brian E., additional, Madden, Jill A., additional, MacArthur, Daniel, additional, Lovgren, Alysia, additional, Lerner-Ellis, Jordan P., additional, Lin, Jasmine, additional, Laing, Nigel, additional, Hildebrandt, Friedhelm, additional, Hentschel, Julia, additional, Groopman, Emily, additional, Goodrich, Julia, additional, Gleeson, Joseph G., additional, Ghaoui, Roula, additional, Genetti, Casie A., additional, Gburek-Augustat, Janina, additional, Gazda, Hanna T., additional, Ganesh, Vijay S., additional, Ganapathi, Mythily, additional, Gallacher, Lyndon, additional, Fu, Jack M., additional, Evangelista, Emily, additional, England, Eleina, additional, Donkervoort, Sandra, additional, DiTroia, Stephanie, additional, Cooper, Sandra T., additional, Chung, Wendy K., additional, Christodoulou, John, additional, Chao, Katherine R., additional, Cato, Liam D., additional, Bujakowska, Kinga M., additional, Bryen, Samantha J., additional, Brand, Harrison, additional, Bönnemann, Carsten G., additional, Beggs, Alan H., additional, Baxter, Samantha M., additional, Bartolomaeus, Tobias, additional, Agrawal, Pankaj B., additional, Talkowski, Michael, additional, Austin-Tse, Christina, additional, Abou Jamra, Rami, additional, Rehm, Heidi L., additional, and O’Donnell-Luria, Anne, additional
Published: 2024
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5. Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes

Author: Karczewski, Konrad J., Solomonson, Matthew, Chao, Katherine R., Goodrich, Julia K., Tiao, Grace, Lu, Wenhan, Riley-Gillis, Bridget M., Tsai, Ellen A., Kim, Hye In, Zheng, Xiuwen, Rahimov, Fedik, Esmaeeli, Sahar, Grundstad, A. Jason, Reppell, Mark, Waring, Jeff, Jacob, Howard, Sexton, David, Bronson, Paola G., Chen, Xing, Hu, Xinli, Goldstein, Jacqueline I., King, Daniel, Vittal, Christopher, Poterba, Timothy, Palmer, Duncan S., Churchhouse, Claire, Howrigan, Daniel P., Zhou, Wei, Watts, Nicholas A., Nguyen, Kevin, Nguyen, Huy, Mason, Cara, Farnham, Christopher, Tolonen, Charlotte, Gauthier, Laura D., Gupta, Namrata, MacArthur, Daniel G., Rehm, Heidi L., Seed, Cotton, Philippakis, Anthony A., Daly, Mark J., Davis, J. Wade, Runz, Heiko, Miller, Melissa R., and Neale, Benjamin M.
Published: 2022
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6. Genome and RNA sequencing boost neuromuscular diagnoses to 62% from 34% with exome sequencing alone

Author: Marchant, Rhett G., primary, Bryen, Samantha J., additional, Bahlo, Melanie, additional, Cairns, Anita, additional, Chao, Katherine R., additional, Corbett, Alastair, additional, Davis, Mark R., additional, Ganesh, Vijay S., additional, Ghaoui, Roula, additional, Jones, Kristi J., additional, Kornberg, Andrew J., additional, Lek, Monkol, additional, Liang, Christina, additional, MacArthur, Daniel G., additional, Oates, Emily C., additional, O'Donnell‐Luria, Anne, additional, O'Grady, Gina L., additional, Osei‐Owusu, Ikeoluwa A., additional, Rafehi, Haloom, additional, Reddel, Stephen W., additional, Roxburgh, Richard H., additional, Ryan, Monique M., additional, Sandaradura, Sarah A., additional, Scott, Liam W., additional, Valkanas, Elise, additional, Weisburd, Ben, additional, Young, Helen, additional, Evesson, Frances J., additional, Waddell, Leigh B., additional, and Cooper, Sandra T., additional
Published: 2024
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7. Differential inclusion of NEB exons 143 and 144 provides insight into NEB-related myopathy variant interpretation and disease manifestation

Author: Silverstein, Sarah, primary, Orbach, Rotem, additional, Syeda, Safoora, additional, Reghan Foley, A, additional, Gorokhova, Svetlana, additional, Meilleur, Katherine G., additional, Leach, Meganne E., additional, Uapinyoying, Prech, additional, Chao, Katherine R, additional, Donkervoort, Sandra, additional, and Bönnemann, Carsten G., additional
Published: 2024
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8. Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis

Author: Mohassel, Payam, Donkervoort, Sandra, Lone, Museer A., Nalls, Matthew, Gable, Kenneth, Gupta, Sita D., Foley, A. Reghan, Hu, Ying, Saute, Jonas Alex Morales, Moreira, Ana Lucila, Kok, Fernando, Introna, Alessandro, Logroscino, Giancarlo, Grunseich, Christopher, Nickolls, Alec R., Pourshafie, Naemeh, Neuhaus, Sarah B., Saade, Dimah, Gangfuß, Andrea, Kölbel, Heike, Piccus, Zoe, Le Pichon, Claire E., Fiorillo, Chiara, Ly, Cindy V., Töpf, Ana, Brady, Lauren, Specht, Sabine, Zidell, Aliza, Pedro, Helio, Mittelmann, Eric, Thomas, Florian P., Chao, Katherine R., Konersman, Chamindra G., Cho, Megan T., Brandt, Tracy, Straub, Volker, Connolly, Anne M., Schara, Ulrike, Roos, Andreas, Tarnopolsky, Mark, Höke, Ahmet, Brown, Robert H., Lee, Chia-Hsueh, Hornemann, Thorsten, Dunn, Teresa M., and Bönnemann, Carsten G.
Published: 2021
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9. BET1 variants establish impaired vesicular transport as a cause for muscular dystrophy with epilepsy

Author: Donkervoort, Sandra, Krause, Niklas, Dergai, Mykola, Yun, Pomi, Koliwer, Judith, Gorokhova, Svetlana, Geist Hauserman, Janelle, Cummings, Beryl B, Hu, Ying, Smith, Rosemarie, Uapinyoying, Prech, Ganesh, Vijay S, Ghosh, Partha S, Monaghan, Kristin G, Edassery, Seby L, Ferle, Pia E, Silverstein, Sarah, Chao, Katherine R, Snyder, Molly, Ellingwood, Sara, Bharucha‐Goebel, Diana, Iannaccone, Susan T, Dal Peraro, Matteo, Foley, A Reghan, Savas, Jeffrey N, Bolduc, Véronique, Fasshauer, Dirk, Bönnemann, Carsten G, and Schwake, Michael
Published: 2021
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10. Recurrent de novoSPTLC2variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis

Author: Syeda, Safoora B, primary, Lone, Museer A, additional, Mohassel, Payam, additional, Donkervoort, Sandra, additional, Munot, Pinki, additional, França, Marcondes C, additional, Galarza-Brito, Juan Eli, additional, Eckenweiler, Matthias, additional, Asamoah, Alexander, additional, Gable, Kenneth, additional, Majumdar, Anirban, additional, Schumann, Anke, additional, Gupta, Sita D, additional, Lakhotia, Arpita, additional, Shieh, Perry B, additional, Foley, A Reghan, additional, Jackson, Kelly E, additional, Chao, Katherine R, additional, Winder, Thomas L, additional, Catapano, Francesco, additional, Feng, Lucy, additional, Kirschner, Janbernd, additional, Muntoni, Francesco, additional, Dunn, Teresa M, additional, Hornemann, Thorsten, additional, and Bönnemann, Carsten G, additional
Published: 2023
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11. Biallelic CRELD1 variants cause a multisystem syndrome including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

Author: Jeffries, Lauren, primary, Mis, Emily K., additional, McWalter, Kirsty, additional, Donkervoort, Sandra, additional, Brodsky, Nina N., additional, Carpier, Jean-Marie, additional, Ji, Weizhen, additional, Ionita, Cristian, additional, Roy, Bhaskar, additional, Morrow, Jon S., additional, Darbinyan, Armine, additional, Iyer, Krishna, additional, Aul, Ritu B., additional, Banka, Siddharth, additional, Chao, Katherine R., additional, Cobbold, Laura, additional, Cohen, Stacey, additional, Custodio, Helena M., additional, Drummond-Borg, Margaret, additional, Elmslie, Frances, additional, Finanger, Erika, additional, Hainline, Bryan E., additional, Helbig, Ingo, additional, Hewson, Stacy, additional, Hu, Ying, additional, Jackson, Adam, additional, Josifova, Dragana, additional, Konstantino, Monica, additional, Leach, Meganne E., additional, Mak, Bryan, additional, McCormick, David, additional, McGee, Elisabeth, additional, Nelson, Stanley, additional, Nguyen, Joanne, additional, Nugent, Kimberly, additional, Ortega, Lucy, additional, Goodkin, Howard P., additional, Roeder, Elizabeth, additional, Roy, Sani, additional, Sapp, Katie, additional, Saade, Dimah, additional, Sisodiya, Sanjay M., additional, Stals, Karen, additional, Towner, Shelley, additional, Wilson, William, additional, Khokha, Mustafa K., additional, Bönnemann, Carsten G., additional, Lucas, Carrie L., additional, Lakhani, Saquib A., additional, Acosta, Maria T., additional, Adam, Margaret, additional, Adams, David R., additional, Agrawal, Pankaj B., additional, Alejandro, Mercedes E., additional, Alvey, Justin, additional, Amendola, Laura, additional, Andrews, Ashley, additional, Ashley, Euan A., additional, Azamian, Mahshid S., additional, Bacino, Carlos A., additional, Bademci, Guney, additional, Baker, Eva, additional, Balasubramanyam, Ashok, additional, Baldridge, Dustin, additional, Bale, Jim, additional, Bamshad, Michael, additional, Barbouth, Deborah, additional, Bayrak-Toydemir, Pinar, additional, Beck, Anita, additional, Beggs, Alan H., additional, Behrens, Edward, additional, Bejerano, Gill, additional, Bennet, Jimmy, additional, Berg-Rood, Beverly, additional, Bernstein, Jonathan A., additional, Berry, Gerard T., additional, Bican, Anna, additional, Bivona, Stephanie, additional, Blue, Elizabeth, additional, Bohnsack, John, additional, Bonnenmann, Carsten, additional, Bonner, Devon, additional, Botto, Lorenzo, additional, Boyd, Brenna, additional, Briere, Lauren C., additional, Brokamp, Elly, additional, Brown, Gabrielle, additional, Burke, Elizabeth A., additional, Burrage, Lindsay C., additional, Butte, Manish J., additional, Byers, Peter, additional, Byrd, William E., additional, Carey, John, additional, Carrasquillo, Olveen, additional, Peter Chang, Ta Chen, additional, Chanprasert, Sirisak, additional, Chao, Hsiao-Tuan, additional, Clark, Gary D., additional, Coakley, Terra R., additional, Cobban, Laurel A., additional, Cogan, Joy D., additional, Coggins, Matthew, additional, Cole, F Sessions, additional, Colley, Heather A., additional, Cooper, Cynthia M., additional, Craigen, William J., additional, Crouse, Andrew B., additional, Cunningham, Michael, additional, D'Souza, Precilla, additional, Dai, Hongzheng, additional, Dasari, Surendra, additional, Davids, Mariska, additional, Dayal, Jyoti G., additional, Deardorff, Matthew, additional, Dell'Angelica, Esteban C., additional, Dhar, Shweta U., additional, Dipple, Katrina, additional, Doherty, Daniel, additional, Dorrani, Naghmeh, additional, Douine, Emilie D., additional, Draper, David D., additional, Duncan, Laura, additional, Earl, Dawn, additional, Eckstein, David J., additional, Emrick, Lisa T., additional, Eng, Christine M., additional, Esteves, Cecilia, additional, Estwick, Tyra, additional, Falk, Marni, additional, Fernandez, Liliana, additional, Ferreira, Carlos, additional, Fieg, Elizabeth L., additional, Findley, Laurie C., additional, Fisher, Paul G., additional, Fogel, Brent L., additional, Forghani, Irman, additional, Fresard, Laure, additional, Gahl, William A., additional, Glass, Ian, additional, Godfrey, Rena A., additional, Golden-Grant, Katie, additional, Goldman, Alica M., additional, Goldstein, David B., additional, Grajewski, Alana, additional, Groden, Catherine A., additional, Gropman, Andrea L., additional, Gutierrez, Irma, additional, Hahn, Sihoun, additional, Hamid, Rizwan, additional, Hanchard, Neil A., additional, Hassey, Kelly, additional, Hayes, Nichole, additional, High, Frances, additional, Hing, Anne, additional, Hisama, Fuki M., additional, Holm, Ingrid A., additional, Hom, Jason, additional, Horike-Pyne, Martha, additional, Huang, Alden, additional, Huang, Yong, additional, Isasi, Rosario, additional, Jamal, Fariha, additional, Jarvik, Gail P., additional, Jarvik, Jeffrey, additional, Jayadev, Suman, additional, Johnston, Jean M., additional, Karaviti, Lefkothea, additional, Kelley, Emily G., additional, Kennedy, Jennifer, additional, Kiley, Dana, additional, Kohane, Isaac S., additional, Kohler, Jennefer N., additional, Krakow, Deborah, additional, Krasnewich, Donna M., additional, Kravets, Elijah, additional, Korrick, Susan, additional, Koziura, Mary, additional, Krier, Joel B., additional, Lalani, Seema R., additional, Lam, Byron, additional, Lam, Christina, additional, Lanpher, Brendan C., additional, Lanza, Ian R., additional, Lau, C Christopher, additional, LeBlanc, Kimberly, additional, Lee, Brendan H., additional, Lee, Hane, additional, Levitt, Roy, additional, Lewis, Richard A., additional, Lincoln, Sharyn A., additional, Liu, Pengfei, additional, Liu, Xue Zhong, additional, Longo, Nicola, additional, Loo, Sandra K., additional, Loscalzo, Joseph, additional, Maas, Richard L., additional, Macnamara, Ellen F., additional, MacRae, Calum A., additional, Maduro, Valerie V., additional, Majcherska, Marta M., additional, Christine V Malicdan, May, additional, Mamounas, Laura A., additional, Manolio, Teri A., additional, Mao, Rong, additional, Maravilla, Kenneth, additional, Markello, Thomas C., additional, Marom, Ronit, additional, Marth, Gabor, additional, Martin, Beth A., additional, Martin, Martin G., additional, Martínez-Agosto, Julian A., additional, Marwaha, Shruti, additional, McCauley, Jacob, additional, McCormack, Colleen E., additional, McCray, Alexa T., additional, Mefford, Heather, additional, Merritt, J Lawrence, additional, Might, Matthew, additional, Mirzaa, Ghayda, additional, Morava, Eva, additional, Moretti, Paolo M., additional, Morimoto, Marie, additional, Mulvihill, John J., additional, Murdock, David R., additional, Nakano-Okuno, Mariko, additional, Nath, Avi, additional, Nelson, Stan F., additional, Newman, John H., additional, Nicholas, Sarah K., additional, Nickerson, Deborah, additional, Nieves-Rodriguez, Shirley, additional, Novacic, Donna, additional, Oglesbee, Devin, additional, Orengo, James P., additional, Pace, Laura, additional, Pak, Stephen, additional, Pallais, J Carl, additional, Papp, Jeanette C., additional, Parker, Neil H., additional, Phillips, John A., additional, Posey, Jennifer E., additional, Potocki, Lorraine, additional, Pusey, Barbara N., additional, Quinlan, Aaron, additional, Raskind, Wendy, additional, Raja, Archana N., additional, Rao, Deepak A., additional, Renteria, Genecee, additional, Reuter, Chloe M., additional, Rives, Lynette, additional, Robertson, Amy K., additional, Rodan, Lance H., additional, Rosenfeld, Jill A., additional, Rosenwasser, Natalie, additional, Ruzhnikov, Maura, additional, Sacco, Ralph, additional, Sampson, Jacinda B., additional, Samson, Susan L., additional, Saporta, Mario, additional, Scott, C Ron, additional, Schaechter, Judy, additional, Schedl, Timothy, additional, Scott, Daryl A., additional, Sharma, Prashant, additional, Shin, Jimann, additional, Signer, Rebecca, additional, Sillari, Catherine H., additional, Silverman, Edwin K., additional, Sinsheimer, Janet S., additional, Sisco, Kathy, additional, Smith, Edward C., additional, Smith, Kevin S., additional, Solem, Emily, additional, Solnica-Krezel, Lilianna, additional, Stoler, Joan M., additional, Stong, Nicholas, additional, Sullivan, Jennifer A., additional, Sun, Angela, additional, Sutton, Shirley, additional, Sweetser, David A., additional, Sybert, Virginia, additional, Tabor, Holly K., additional, Tamburro, Cecelia P., additional, Tekin, Mustafa, additional, Telischi, Fred, additional, Thorson, Willa, additional, Tifft, Cynthia J., additional, Toro, Camilo, additional, Tran, Alyssa A., additional, Tucker, Brianna M., additional, Urv, Tiina K., additional, Vanderver, Adeline, additional, Velinder, Matt, additional, Viskochil, Dave, additional, Vogel, Tiphanie P., additional, Wahl, Colleen E., additional, Wallace, Stephanie, additional, Walley, Nicole M., additional, Walsh, Chris A., additional, Walker, Melissa, additional, Wambach, Jennifer, additional, Wan, Jijun, additional, Wang, Lee-Kai, additional, Wangler, Michael F., additional, Ward, Patricia A., additional, Wegner, Daniel, additional, Wener, Mark, additional, Wenger, Tara, additional, Perry, Katherine Wesseling, additional, Westerfield, Monte, additional, Wheeler, Matthew T., additional, Whitlock, Jordan, additional, Wolfe, Lynne A., additional, Woods, Jeremy D., additional, Yamamoto, Shinya, additional, Yang, John, additional, Yu, Guoyun, additional, Zastrow, Diane B., additional, Zhao, Chunli, additional, Zuchner, Stephan, additional, Ambrose, J.C., additional, Arumugam, P., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, FurióTarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Hamblin, A., additional, Henderson, S., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Ibáñez, K., additional, Jackson, R., additional, Jones, L.J., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, MaleadyCrowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, and Witkowska, K., additional
Published: 2023
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12. Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease

Author: Lemire, Gabrielle, primary, Sanchis-Juan, Alba, additional, Russell, Kathryn, additional, Baxter, Samantha, additional, Chao, Katherine R., additional, Singer-Berk, Moriel, additional, Groopman, Emily, additional, Wong, Isaac, additional, England, Eleina, additional, Goodrich, Julia, additional, Pais, Lynn, additional, Austin-Tse, Christina, additional, DiTroia, Stephanie, additional, O’Heir, Emily, additional, Ganesh, Vijay S., additional, Wojcik, Monica H., additional, Evangelista, Emily, additional, Snow, Hana, additional, Osei-Owusu, Ikeoluwa, additional, Fu, Jack, additional, Singh, Mugdha, additional, Mostovoy, Yulia, additional, Huang, Steve, additional, Garimella, Kiran, additional, Kirkham, Samantha L., additional, Neil, Jennifer E., additional, Shao, Diane D., additional, Walsh, Christopher A., additional, Argili, Emanuela, additional, Le, Carolyn, additional, Sherr, Elliott H., additional, Gleeson, Joseph, additional, Shril, Shirlee, additional, Schneider, Ronen, additional, Hildebrandt, Friedhelm, additional, Sankaran, Vijay G., additional, Madden, Jill A., additional, Genetti, Casie A., additional, Beggs, Alan H., additional, Agrawal, Pankaj B., additional, Bujakowska, Kinga M., additional, Place, Emily, additional, Pierce, Eric A., additional, Donkervoort, Sandra, additional, Bönnemann, Carsten G., additional, Gallacher, Lyndon, additional, Stark, Zornitza, additional, Tan, Tiong, additional, White, Susan M., additional, Töpf, Ana, additional, Straub, Volker, additional, Fleming, Mark D., additional, Pollak, Martin R., additional, Õunap, Katrin, additional, Pajusalu, Sander, additional, Donald, Kirsten A., additional, Bruwer, Zandre, additional, Ravenscroft, Gianina, additional, Laing, Nigel G., additional, MacArthur, Daniel G., additional, Rehm, Heidi L., additional, Talkowski, Michael E., additional, Brand, Harrison, additional, and O’Donnell-Luria, Anne, additional
Published: 2023
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13. Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

Author: Wojcik, Monica H, primary, Lemire, Gabrielle, additional, Zaki, Maha S, additional, Wissmann, Mariel, additional, Win, Wathone, additional, White, Sue, additional, Weisburd, Ben, additional, Waddell, Leigh B, additional, Verboon, Jeffrey M, additional, VanNoy, Grace E, additional, Topf, Ana, additional, Tan, Tiong Yang, additional, Straub, Volker, additional, Stenton, Sarah L, additional, Snow, Hana, additional, Singer-Berk, Moriel, additional, Silver, Josh, additional, Shril, Shirlee, additional, Seaby, Eleanor G, additional, Schneider, Ronen, additional, Sankaran, Vijay G, additional, Sanchis-Juan, Alba, additional, Russell, Kathryn A, additional, Reinson, Karit, additional, Ravenscroft, Gina, additional, Pierce, Eric A, additional, Place, Emily M, additional, Pajusalu, Sander, additional, Pais, Lynn, additional, Ounap, Katrin, additional, Osei-Owusu, Ikeoluwa, additional, Okur, Volkan, additional, Oja, Kaisa Teele, additional, OLeary, Melanie, additional, OHeir, Emily, additional, Morel, Chantal, additional, Marchant, Rhett G, additional, Mangilog, Brian E, additional, Madden, Jill A, additional, MacArthur, Daniel, additional, Lovgren, Alysia, additional, Lerner-Ellis, Jordan P, additional, Lin, Jasmine, additional, Laing, Nigel, additional, Hildebrandt, Friedhelm, additional, Groopman, Emily, additional, Goodrich, Julia, additional, Gleeson, Joseph G, additional, Ghaoui, Roula, additional, Genetti, Casie A, additional, Gazda, Hanna, additional, Ganesh, Vijay S, additional, Ganapathi, Mythily, additional, Gallacher, Lyndon, additional, Fu, Jack, additional, Evangelista, Emily, additional, England, Eleina, additional, Donkervoort, Sandra, additional, DiTroia, Stephanie, additional, Cooper, Sandra T, additional, Chung, Wendy K, additional, Christodoulou, John, additional, Chao, Katherine R, additional, Cato, Liam D, additional, Bujakowska, Kinga M, additional, Bryen, Samantha J, additional, Brand, Harrison, additional, Bonnemann, Carsten, additional, Beggs, Alan H, additional, Baxter, Samantha M, additional, Agrawal, Pankaj B, additional, Talkowski, Michael, additional, Austin-Tse, Christina, additional, Rehm, Heidi L, additional, and ODonnell-Luria, Anne, additional
Published: 2023
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14. Recurrent de novo SPTLC2 variant causes childhoodonset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis.

Author: Syeda, Safoora B., Lone, Museer A., Mohassel, Payam, Donkervoort, Sandra, Munot, Pinki, França Jr., Marcondes C., Galarza-Brito, Juan Eli, Eckenweiler, Matthias, Asamoah, Alexander, Gable, Kenneth, Majumdar, Anirban, Schumann, Anke, Gupta, Sita D., Lakhotia, Arpita, Shieh, Perry B., Foley, A. Reghan, Jackson, Kelly E., Chao, Katherine R., Winder, Thomas L., and Catapano, Francesco
Subjects: AMYOTROPHIC lateral sclerosis, SPASTICITY, FAMILIAL spastic paraplegia, LIQUID chromatography-mass spectrometry
Published: 2024
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15. Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy

Author: Morales-Rosado, Joel A., primary, Schwab, Tanya L., additional, Macklin-Mantia, Sarah K., additional, Foley, A. Reghan, additional, Pinto e Vairo, Filippo, additional, Pehlivan, Davut, additional, Donkervoort, Sandra, additional, Rosenfeld, Jill A., additional, Boyum, Grace E., additional, Hu, Ying, additional, Cong, Anh T.Q., additional, Lotze, Timothy E., additional, Mohila, Carrie A., additional, Saade, Dimah, additional, Bharucha-Goebel, Diana, additional, Chao, Katherine R., additional, Grunseich, Christopher, additional, Bruels, Christine C., additional, Littel, Hannah R., additional, Estrella, Elicia A., additional, Pais, Lynn, additional, Kang, Peter B., additional, Zimmermann, Michael T., additional, Lupski, James R., additional, Lee, Brendan, additional, Schellenberg, Matthew J., additional, Clark, Karl J., additional, Wierenga, Klaas J., additional, Bönnemann, Carsten G., additional, and Klee, Eric W., additional
Published: 2023
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16. A harmonized public resource of deeply sequenced diverse human genomes

Author: Koenig, Zan, Yohannes, Mary T., Nkambule, Lethukuthula L., Zhao, Xuefang, Goodrich, Julia K., Kim, Heesu Ally, Wilson, Michael W., Tiao, Grace, Hao, Stephanie P., Sahakian, Nareh, Chao, Katherine R., Walker, Mark A., Lyu, Yunfei, Rehm, Heidi L., Neale, Benjamin M., Talkowski, Michael E., Daly, Mark J., Brand, Harrison, Karczewski, Konrad J., Atkinson, Elizabeth G., and Martin, Alicia R.
Abstract: Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also show substantial added value from this data set compared with the prior versions of the component resources, typically combined via liftOver and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared with previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality-control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.
Published: 2024
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17. Recurrent de novo SPTLC2variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis

Author: Syeda, Safoora B, Lone, Museer A, Mohassel, Payam, Donkervoort, Sandra, Munot, Pinki, Franca, Marcondes C, Galarza-Brito, Juan Eli, Eckenweiler, Matthias, Asamoah, Alexander, Gable, Kenneth, Majumdar, Anirban, Schumann, Anke, Gupta, Sita D, Lakhotia, Arpita, Shieh, Perry B, Foley, A Reghan, Jackson, Kelly E, Chao, Katherine R, Winder, Thomas L, Catapano, Francesco, Feng, Lucy, Kirschner, Janbernd, Muntoni, Francesco, Dunn, Teresa M, Hornemann, Thorsten, and Bo¨nnemann, Carsten G
Abstract: BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2c.778G>A [p.Glu260Lys] manifesting with juvenile ALS.MethodsClinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients’ blood and fibroblasts, was performed.ResultsAll patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS.ConclusionsSPTLC2is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.
Published: 2024
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18. A harmonized public resource of deeply sequenced diverse human genomes

Author: Koenig, Zan, Yohannes, Mary T., Nkambule, Lethukuthula L., Goodrich, Julia K., Kim, Heesu Ally, Zhao, Xuefang, Wilson, Michael W., Tiao, Grace, Hao, Stephanie P., Sahakian, Nareh, Chao, Katherine R., Talkowski, Michael E., Daly, Mark J., Brand, Harrison, Karczewski, Konrad J., Atkinson, Elizabeth G., and Martin, Alicia R.
Subjects: Article
Abstract: Underrepresented populations are often excluded from genomic studies due in part to a lack of resources supporting their analysis. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high quality set of 4,096 whole genomes from HGDP and 1kGP with data from gnomAD and identified over 155 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also demonstrate substantial added value from this dataset compared to the prior versions of the component resources, typically combined via liftover and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared to previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.
Published: 2023

19. Germline GATA1s-generating mutations predispose to leukemia with acquired trisomy 21 and Down syndrome-like phenotype

Author: Hasle, Henrik, Kline, Ronald M., Kjeldsen, Eigil, Nik-Abdul-Rashid, Nik F., Bhojwani, Deepa, Verboon, Jeffrey M., DiTroia, Stephanie P., Chao, Katherine R., Raaschou-Jensen, Klas, Palle, Josefine, Zwaan, C. Michel, Nyvold, Charlotte Guldborg, Sankaran, Vijay G., Cantor, Alan B., Hasle, Henrik, Kline, Ronald M., Kjeldsen, Eigil, Nik-Abdul-Rashid, Nik F., Bhojwani, Deepa, Verboon, Jeffrey M., DiTroia, Stephanie P., Chao, Katherine R., Raaschou-Jensen, Klas, Palle, Josefine, Zwaan, C. Michel, Nyvold, Charlotte Guldborg, Sankaran, Vijay G., and Cantor, Alan B.
Abstract: Individuals with Down syndrome are at increased risk of myeloid leukemia in early childhood, which is associated with acquisition of GATA1 mutations that generate a short GATA1 isoform called GATA1s. Germline GATA1s-generating mutations result in congenital anemia in males. We report on 2 unrelated families that harbor germline GATA1s-generating mutations in which several members developed acute megakaryoblastic leukemia in early childhood. All evaluable leukemias had acquired trisomy 21 or tetrasomy 21. The leukemia characteristics overlapped with those of myeloid leukemia associated with Down syndrome, including age of onset at younger than 4 years, unique immunophenotype, complex karyotype, gene expression patterns, and drug sensitivity. These findings demonstrate that the combination of trisomy 21 and GATA1s-generating mutations results in a unique myeloid leukemia independent of whether the GATA1 mutation or trisomy 21 is the primary or secondary event and suggest that there is a unique functional cooperation between GATA1s and trisomy 21 in leukemogenesis. The family histories also indicate that germline GATA1s-generating mutations should be included among those associated with familial predisposition for myelodysplastic syndrome and leukemia.
Published: 2022
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20. Germline GATA1s-generating mutations predispose to leukemia with acquired trisomy 21 and Down syndrome-like phenotype

Author: Hasle, Henrik, primary, Kline, Ronald M., additional, Kjeldsen, Eigil, additional, Nik-Abdul-Rashid, Nik F., additional, Bhojwani, Deepa, additional, Verboon, Jeffrey M., additional, DiTroia, Stephanie P., additional, Chao, Katherine R., additional, Raaschou-Jensen, Klas, additional, Palle, Josefine, additional, Zwaan, C. Michel, additional, Nyvold, Charlotte Guldborg, additional, Sankaran, Vijay G., additional, and Cantor, Alan B., additional
Published: 2022
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21. Recognizable Pattern of Arthrogryposis and Congenital Myopathy Caused by the Recurrent TTN Metatranscript-only c.39974-11T > G Splice Variant

Author: Averdunk, Luisa, additional, Donkervoort, Sandra, additional, Horn, Denise, additional, Waldmüller, Stephan, additional, Syeda, Safoora, additional, Neuhaus, Sarah B., additional, Chao, Katherine R., additional, van Riesen, Anne, additional, Gauck, Darja, additional, Haack, Tobias, additional, Japp, Anna S., additional, Lee, Unaa, additional, Bönnemann, Carsten G., additional, Mayatepek, Ertan, additional, and Distelmaier, Felix, additional
Published: 2022
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22. Biallelic variants in TAMM41 are associated with low muscle cardiolipin levels, leading to neonatal mitochondrial disease

Author: Thompson, Kyle, primary, Bianchi, Lucas, additional, Rastelli, Francesca, additional, Piron-Prunier, Florence, additional, Ayciriex, Sophie, additional, Besmond, Claude, additional, Hubert, Laurence, additional, Barth, Magalie, additional, Barbosa, Inês A., additional, Deshpande, Charu, additional, Chitre, Manali, additional, Mehta, Sarju G., additional, Wever, Eric J.M., additional, Marcorelles, Pascale, additional, Donkervoort, Sandra, additional, Saade, Dimah, additional, Bönnemann, Carsten G., additional, Chao, Katherine R., additional, Cai, Chunyu, additional, Iannaccone, Susan T., additional, Dean, Andrew F., additional, McFarland, Robert, additional, Vaz, Frédéric M., additional, Delahodde, Agnès, additional, Taylor, Robert W., additional, and Rötig, Agnès, additional
Published: 2022
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23. Centers for Mendelian Genomics: A decade of facilitating gene discovery

Author: Baxter, Samantha M., primary, Posey, Jennifer E., additional, Lake, Nicole J., additional, Sobreira, Nara, additional, Chong, Jessica X., additional, Buyske, Steven, additional, Blue, Elizabeth E., additional, Chadwick, Lisa H., additional, Coban-Akdemir, Zeynep H., additional, Doheny, Kimberly F., additional, Davis, Colleen P., additional, Lek, Monkol, additional, Wellington, Christopher, additional, Jhangiani, Shalini N., additional, Gerstein, Mark, additional, Gibbs, Richard A., additional, Lifton, Richard P., additional, MacArthur, Daniel G., additional, Matise, Tara C., additional, Lupski, James R., additional, Valle, David, additional, Bamshad, Michael J., additional, Hamosh, Ada, additional, Mane, Shrikant, additional, Nickerson, Deborah A., additional, Rehm, Heidi L., additional, O’Donnell-Luria, Anne, additional, Adams, Marcia, additional, Aguet, François, additional, Akay, Gulsen, additional, Anderson, Peter, additional, Antonescu, Corina, additional, Arachchi, Harindra M., additional, Atik, Mehmed M., additional, Austin-Tse, Christina A., additional, Babb, Larry, additional, Bacus, Tamara J., additional, Bahrambeigi, Vahid, additional, Balasubramanian, Suganthi, additional, Bayram, Yavuz, additional, Beaudet, Arthur L., additional, Beck, Christine R., additional, Belmont, John W., additional, Below, Jennifer E., additional, Bilguvar, Kaya, additional, Boehm, Corinne D., additional, Boerwinkle, Eric, additional, Boone, Philip M., additional, Bowne, Sara J., additional, Brand, Harrison, additional, Buckingham, Kati J., additional, Byrne, Alicia B., additional, Calame, Daniel, additional, Campbell, Ian M., additional, Cao, Xiaolong, additional, Carvalho, Claudia, additional, Chander, Varuna, additional, Chang, Jaime, additional, Chao, Katherine R., additional, Chinn, Ivan K., additional, Clarke, Declan, additional, Collins, Ryan L., additional, Cummings, Beryl, additional, Dardas, Zain, additional, Dawood, Moez, additional, Delano, Kayla, additional, DiTroia, Stephanie P., additional, Doddapaneni, Harshavardhan, additional, Du, Haowei, additional, Du, Renqian, additional, Duan, Ruizhi, additional, Eldomery, Mohammad, additional, Eng, Christine M., additional, England, Eleina, additional, Evangelista, Emily, additional, Everett, Selin, additional, Fatih, Jawid, additional, Felsenfeld, Adam, additional, Francioli, Laurent C., additional, Frazar, Christian D., additional, Fu, Jack, additional, Gamarra, Emmanuel, additional, Gambin, Tomasz, additional, Gan, Weiniu, additional, Gandhi, Mira, additional, Ganesh, Vijay S., additional, Garimella, Kiran V., additional, Gauthier, Laura D., additional, Giroux, Danielle, additional, Gonzaga-Jauregui, Claudia, additional, Goodrich, Julia K., additional, Gordon, William W., additional, Griffith, Sean, additional, Grochowski, Christopher M., additional, Gu, Shen, additional, Gudmundsson, Sanna, additional, Hall, Stacey J., additional, Hansen, Adam, additional, Harel, Tamar, additional, Harmanci, Arif O., additional, Herman, Isabella, additional, Hetrick, Kurt, additional, Hijazi, Hadia, additional, Horike-Pyne, Martha, additional, Hsu, Elvin, additional, Hu, Jianhong, additional, Huang, Yongqing, additional, Hurless, Jameson R., additional, Jahl, Steve, additional, Jarvik, Gail P., additional, Jiang, Yunyun, additional, Johanson, Eric, additional, Jolly, Angad, additional, Karaca, Ender, additional, Khayat, Michael, additional, Knight, James, additional, Kolar, J. Thomas, additional, Kumar, Sushant, additional, Lalani, Seema, additional, Laricchia, Kristen M., additional, Larkin, Kathryn E., additional, Leal, Suzanne M., additional, Lemire, Gabrielle, additional, Lewis, Richard A., additional, Li, He, additional, Ling, Hua, additional, Lipson, Rachel B., additional, Liu, Pengfei, additional, Lovgren, Alysia Kern, additional, López-Giráldez, Francesc, additional, MacMillan, Melissa P., additional, Mangilog, Brian E., additional, Mano, Stacy, additional, Marafi, Dana, additional, Marosy, Beth, additional, Marshall, Jamie L., additional, Martin, Renan, additional, Marvin, Colby T., additional, Mawhinney, Michelle, additional, McGee, Sean, additional, McGoldrick, Daniel J., additional, Mehaffey, Michelle, additional, Mekonnen, Betselote, additional, Meng, Xiaolu, additional, Mitani, Tadahiro, additional, Miyake, Christina Y., additional, Mohr, David, additional, Morris, Shaine, additional, Mullen, Thomas E., additional, Murdock, David R., additional, Murugan, Mullai, additional, Muzny, Donna M., additional, Myers, Ben, additional, Neira, Juanita, additional, Nguyen, Kevin K., additional, Nielsen, Patrick M., additional, Nudelman, Natalie, additional, O’Heir, Emily, additional, O’Leary, Melanie C., additional, Ongaco, Chrissie, additional, Orange, Jordan, additional, Osei-Owusu, Ikeoluwa A., additional, Paine, Ingrid S., additional, Pais, Lynn S., additional, Paschall, Justin, additional, Patterson, Karynne, additional, Pehlivan, Davut, additional, Pelle, Benjamin, additional, Penney, Samantha, additional, Perez de Acha Chavez, Jorge, additional, Pierce-Hoffman, Emma, additional, Poli, Cecilia M., additional, Punetha, Jaya, additional, Radhakrishnan, Aparna, additional, Richardson, Matthew A., additional, Rodrigues, Eliete, additional, Roote, Gwendolin T., additional, Rosenfeld, Jill A., additional, Ryke, Erica L., additional, Sabo, Aniko, additional, Sanchez, Alice, additional, Schrauwen, Isabelle, additional, Scott, Daryl A., additional, Sedlazeck, Fritz, additional, Serrano, Jillian, additional, Shaw, Chad A., additional, Shelford, Tameka, additional, Shively, Kathryn M., additional, Singer-Berk, Moriel, additional, Smith, Joshua D., additional, Snow, Hana, additional, Snyder, Grace, additional, Solomonson, Matthew, additional, Son, Rachel G., additional, Song, Xiaofei, additional, Stankiewicz, Pawel, additional, Stephan, Taylorlyn, additional, Sutton, V. Reid, additional, Sveden, Abigail, additional, Sánchez, Diana Cornejo, additional, Tackett, Monica, additional, Talkowski, Michael, additional, Threlkeld, Machiko S., additional, Tiao, Grace, additional, Udler, Miriam S., additional, Vail, Laura, additional, Valivullah, Zaheer, additional, Valkanas, Elise, additional, VanNoy, Grace E., additional, Wang, Qingbo S., additional, Wang, Gao, additional, Wang, Lu, additional, Wangler, Michael F., additional, Watts, Nicholas A., additional, Weisburd, Ben, additional, Weiss, Jeffrey M., additional, Wheeler, Marsha M., additional, White, Janson J., additional, Williamson, Clara E., additional, Wilson, Michael W., additional, Wiszniewski, Wojciech, additional, Withers, Marjorie A., additional, Witmer, Dane, additional, Witzgall, Lauren, additional, Wohler, Elizabeth, additional, Wojcik, Monica H., additional, Wong, Isaac, additional, Wood, Jordan C., additional, Wu, Nan, additional, Xing, Jinchuan, additional, Yang, Yaping, additional, Yi, Qian, additional, Yuan, Bo, additional, Zeiger, Jordan E., additional, Zhang, Chaofan, additional, Zhang, Peng, additional, Zhang, Yan, additional, Zhang, Xiaohong, additional, Zhang, Yeting, additional, Zhang, Shifa, additional, Zoghbi, Huda, additional, and van den Veyver, Igna, additional
Published: 2022
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24. seqr : A web‐based analysis and collaboration tool for rare disease genomics

Author: Pais, Lynn S., primary, Snow, Hana, additional, Weisburd, Ben, additional, Zhang, Shifa, additional, Baxter, Samantha M., additional, DiTroia, Stephanie, additional, O'Heir, Emily, additional, England, Eleina, additional, Chao, Katherine R., additional, Lemire, Gabrielle, additional, Osei‐Owusu, Ikeoluwa, additional, VanNoy, Grace E., additional, Wilson, Michael, additional, Nguyen, Kevin, additional, Arachchi, Harindra, additional, Phu, William, additional, Solomonson, Matthew, additional, Mano, Stacy, additional, O'Leary, Melanie, additional, Lovgren, Alysia, additional, Babb, Lawrence, additional, Austin‐Tse, Christina A., additional, Rehm, Heidi L., additional, MacArthur, Daniel G., additional, and O'Donnell‐Luria, Anne, additional
Published: 2022
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25. The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK)

Author: Zampaglione, Erin, primary, Maher, Matthew, additional, Place, Emily M., additional, Wagner, Naomi E., additional, DiTroia, Stephanie, additional, Chao, Katherine R., additional, England, Eleina, additional, CMG, Broad, additional, Catomeris, Andrew, additional, Nassiri, Sherwin, additional, Himes, Seraphim, additional, Pagliarulo, Joey, additional, Ferguson, Charles, additional, Galdikaité-Braziené, Eglé, additional, Cole, Brian, additional, Pierce, Eric A., additional, and Bujakowska, Kinga M., additional
Published: 2022
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26. Disruption of Golgi morphology and altered protein glycosylation in PLA2G6-associated neurodegeneration

Author: Davids, Mariska, Kane, Megan S, He, Miao, Wolfe, Lynne A, Li, Xueli, Raihan, Mohd A, Chao, Katherine R, Bone, William P, Boerkoel, Cornelius F, Gahl, William A, and Toro, Camilo
Published: 2016
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27. A Hidden Structural Variation in a Known IRD Gene: A Cautionary Tale of Two New Disease Candidate Genes

Author: Scott, Hilary A, primary, Larson, Anna, additional, Rong, Shi Song, additional, Mehrotra, Sudeep, additional, Butcher, Rossano, additional, Chao, Katherine R, additional, Wiggs, Janey, additional, Place, Emily M., additional, Pierce, Eric A, additional, and Bujakowska, Kinga M, additional
Published: 2021
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28. Systematic single-variant and gene-based association testing of thousands of phenotypes in 426,370 UK Biobank exomes

Author: Karczewski, Konrad J., primary, Solomonson, Matthew, additional, Chao, Katherine R., additional, Goodrich, Julia K., additional, Tiao, Grace, additional, Lu, Wenhan, additional, Riley-Gillis, Bridget M., additional, Tsai, Ellen A., additional, Kim, Hye In, additional, Zheng, Xiuwen, additional, Rahimov, Fedik, additional, Esmaeeli, Sahar, additional, Grundstad, A. Jason, additional, Reppell, Mark, additional, Waring, Jeff, additional, Jacob, Howard, additional, Sexton, David, additional, Bronson, Paola G., additional, Chen, Xing, additional, Hu, Xinli, additional, Goldstein, Jacqueline I., additional, King, Daniel, additional, Vittal, Christopher, additional, Poterba, Timothy, additional, Palmer, Duncan S., additional, Churchhouse, Claire, additional, Howrigan, Daniel P., additional, Zhou, Wei, additional, Watts, Nicholas A., additional, Nguyen, Kevin, additional, Nguyen, Huy, additional, Mason, Cara, additional, Farnham, Christopher, additional, Tolonen, Charlotte, additional, Gauthier, Laura D., additional, Gupta, Namrata, additional, MacArthur, Daniel G., additional, Rehm, Heidi L., additional, Seed, Cotton, additional, Philippakis, Anthony A., additional, Daly, Mark J., additional, Davis, J. Wade, additional, Runz, Heiko, additional, Miller, Melissa R., additional, and Neale, Benjamin M., additional
Published: 2021
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29. A form of muscular dystrophy associated with pathogenic variants in JAG2

Author: Coppens, Sandra, primary, Barnard, Alison M., additional, Puusepp, Sanna, additional, Pajusalu, Sander, additional, Õunap, Katrin, additional, Vargas-Franco, Dorianmarie, additional, Bruels, Christine C., additional, Donkervoort, Sandra, additional, Pais, Lynn, additional, Chao, Katherine R., additional, Goodrich, Julia K., additional, England, Eleina M., additional, Weisburd, Ben, additional, Ganesh, Vijay S., additional, Gudmundsson, Sanna, additional, O’Donnell-Luria, Anne, additional, Nigul, Mait, additional, Ilves, Pilvi, additional, Mohassel, Payam, additional, Siddique, Teepu, additional, Milone, Margherita, additional, Nicolau, Stefan, additional, Maroofian, Reza, additional, Houlden, Henry, additional, Hanna, Michael G., additional, Quinlivan, Ros, additional, Toosi, Mehran Beiraghi, additional, Karimiani, Ehsan Ghayoor, additional, Costagliola, Sabine, additional, Deconinck, Nicolas, additional, Kadhim, Hazim, additional, Macke, Erica, additional, Lanpher, Brendan C., additional, Klee, Eric W., additional, Łusakowska, Anna, additional, Kostera-Pruszczyk, Anna, additional, Hahn, Andreas, additional, Schrank, Bertold, additional, Nishino, Ichizo, additional, Ogasawara, Masashi, additional, El Sherif, Rasha, additional, Stojkovic, Tanya, additional, Nelson, Isabelle, additional, Bonne, Gisèle, additional, Cohen, Enzo, additional, Boland-Augé, Anne, additional, Deleuze, Jean-François, additional, Meng, Yao, additional, Töpf, Ana, additional, Vilain, Catheline, additional, Pacak, Christina A., additional, Rivera-Zengotita, Marie L., additional, Bönnemann, Carsten G., additional, Straub, Volker, additional, Handford, Penny A., additional, Draper, Isabelle, additional, Walter, Glenn A., additional, and Kang, Peter B., additional
Published: 2021
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30. Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

Author: Wright, Caroline F., primary, Quaife, Nicholas M., additional, Ramos-Hernández, Laura, additional, Danecek, Petr, additional, Ferla, Matteo P., additional, Samocha, Kaitlin E., additional, Kaplanis, Joanna, additional, Gardner, Eugene J., additional, Eberhardt, Ruth Y., additional, Chao, Katherine R., additional, Karczewski, Konrad J., additional, Morales, Joannella, additional, Gallone, Giuseppe, additional, Balasubramanian, Meena, additional, Banka, Siddharth, additional, Gompertz, Lianne, additional, Kerr, Bronwyn, additional, Kirby, Amelia, additional, Lynch, Sally A., additional, Morton, Jenny E.V., additional, Pinz, Hailey, additional, Sansbury, Francis H., additional, Stewart, Helen, additional, Zuccarelli, Britton D., additional, Cook, Stuart A., additional, Taylor, Jenny C., additional, Juusola, Jane, additional, Retterer, Kyle, additional, Firth, Helen V., additional, Hurles, Matthew E., additional, Lara-Pezzi, Enrique, additional, Barton, Paul J.R., additional, and Whiffin, Nicola, additional
Published: 2021
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31. Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript

Author: Wahlster, Lara, primary, Verboon, Jeffrey M., additional, Ludwig, Leif S., additional, Black, Susan C., additional, Luo, Wendy, additional, Garg, Kopal, additional, Voit, Richard A., additional, Collins, Ryan L., additional, Garimella, Kiran, additional, Costello, Maura, additional, Chao, Katherine R., additional, Goodrich, Julia K., additional, DiTroia, Stephanie P., additional, O’Donnell-Luria, Anne, additional, Talkowski, Michael E., additional, Michelson, Alan D., additional, Cantor, Alan B., additional, and Sankaran, Vijay G., additional
Published: 2021
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32. genetic diagnosis; limb-girdle weakness; neuromuscular disease; next-generation sequencing; targeted exome analysisweakness

Author: Töpf, Ana, Johnson, Katherine, Bates, Adam, Phillips, Lauren, Chao, Katherine R., England, Eleina M., Laricchia, Kristen M., Mullen, Thomas, Valkanas, Elise, Xu, Liwen, Bertoli, Marta, Blain, Alison, Casasús, Ana B., Duff, Jennifer, Mroczek, Magdalena, Specht, Sabine, Lek, Monkol, Ensini, Monica, MacArthur, Daniel G., Akay, Ela, Alonso-Pérez, Jorge, Baets, Jonathan, Barisic, Nina, Bastian, Alexandra, Borell, Sabine, Chamova, Teodora, Claeys, Kristl, Colomer, Jaume, Coppens, Sandra, Deconinck, Nicolas, de Ridder, Willem, Díaz-Manera, Jordi, Domínguez-González, Cristina, Duncan, Alexis, Durmus, Hacer, Fahmy, Nagia A., Farrugia, Maria Elena, Fernández-Torrón, Roberto, Gonzalez- Quereda, Lidia, Haberlova, Jana, von der Hagen, Maja, Hahn, Andreas, Jakovčević, Antonia, Jerico Pascual, Ivonne, Kapetanovic, Solange, Kenina, Viktorija, Kirschner, Janbernd, Klein, Andrea, Kölbel, Heike, Kostera-Pruszczyk, Anna, Kulshrestha, Richa, Lähdetie, Jaana, Layegh, Mahsa, Longman, Cheryl, López de Munain, Adolfo, Loscher, Wolfgang, Lusakowska, Anna, Maddison, Paul, Magot, Armelle, Majumdar, Anirban, Martí, Pilar, Martínez Arroyo, Amaia, Mazanec, Radim, Mercier, Sandra, Mongini, Tiziana, Muelas, Nuria, Nascimento, Andrés, Nafissi, Shahriar, Omidi, Shirin, Ortez, Carlos, Paquay, Stéphanie, Pereon, Yann, Perić, Stojan, Ponzalino, Valentina, Rakočević Stojanović, Vidosava, Remiche, Gauthier, Rodríguez Sainz, Aida, Rudnik, Sabine, Sanchez Albisua, Iciar, Santos, Manuela, Schara, Ulrike, Shatillo, Andriy, Sertić, Jadranka, Stephani, Ulrich, Strang- Karlsson, Sonja, Sznajer, Yves, Tanev, Ani, Tournev, Ivailo, Van den Bergh, Peter, Van Parijs, Vinciane, Vílchez, Juan, Vill, Katharina, Vissing, John, Wallgren-Pettersson, Carina, Wanschitz, Julia, Willis, Tracey, Witting, Nanna, Zulaica, Miren, and Straub, Volker
Subjects: genetic diagnosis, limb-girdle weakness, neuromuscular disease, next-generation sequencing, targeted exome analysis
Abstract: Purpose: Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Methods: Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers ; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. Results: We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases ; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Conclusion: Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes. .
Published: 2020

33. Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores

Author: Donkervoort, Sandra, Kutzner, Carl E., Hu, Ying, Lornage, Xaviere, Rendu, John, Stojkovic, Tanya, Baets, Jonathan, Neuhaus, Sarah B., Tanboon, Jantima, Maroofian, Reza, Bolduc, Veronique, Mroczek, Magdalena, Conijn, Stefan, Kuntz, Nancy L., Topf, Ana, Monges, Soledad, Lubieniecki, Fabiana, McCarty, Riley M., Chao, Katherine R., Governali, Serena, Bohm, Johann, Boonyapisit, Kanokwan, Malfatti, Edoardo, Sangruchi, Tumtip, Horkayne-Szakaly, Iren, Hedberg-Oldfors, Carola, Efthymiou, Stephanie, Noguchi, Satoru, Djeddi, Sarah, Iida, Aritoshi, di Rosa, Gabriella, Fiorillo, Chiara, Salpietro, Vincenzo, Darin, Niklas, Faure, Julien, Houlden, Henry, Oldfors, Anders, Nishino, Ichizo, de Ridder, Willem, Straub, Volker, Pokrzywa, Wojciech, Laporte, Jocelyn, Foley, A. Reghan, Romero, Norma B., Ottenheijm, Coen, Hoppe, Thorsten, Boennemann, Carsten G., Donkervoort, Sandra, Kutzner, Carl E., Hu, Ying, Lornage, Xaviere, Rendu, John, Stojkovic, Tanya, Baets, Jonathan, Neuhaus, Sarah B., Tanboon, Jantima, Maroofian, Reza, Bolduc, Veronique, Mroczek, Magdalena, Conijn, Stefan, Kuntz, Nancy L., Topf, Ana, Monges, Soledad, Lubieniecki, Fabiana, McCarty, Riley M., Chao, Katherine R., Governali, Serena, Bohm, Johann, Boonyapisit, Kanokwan, Malfatti, Edoardo, Sangruchi, Tumtip, Horkayne-Szakaly, Iren, Hedberg-Oldfors, Carola, Efthymiou, Stephanie, Noguchi, Satoru, Djeddi, Sarah, Iida, Aritoshi, di Rosa, Gabriella, Fiorillo, Chiara, Salpietro, Vincenzo, Darin, Niklas, Faure, Julien, Houlden, Henry, Oldfors, Anders, Nishino, Ichizo, de Ridder, Willem, Straub, Volker, Pokrzywa, Wojciech, Laporte, Jocelyn, Foley, A. Reghan, Romero, Norma B., Ottenheijm, Coen, Hoppe, Thorsten, and Boennemann, Carsten G.
Abstract: The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization.
Published: 2020

34. Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.

Author: UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, UCL - (SLuc) Service de neurologie pédiatrique, Töpf, Ana, Johnson, Katherine, Bates, Adam, Phillips, Lauren, Chao, Katherine R, England, Eleina M, Laricchia, Kristen M, Mullen, Thomas, Valkanas, Elise, Xu, Liwen, Bertoli, Marta, Blain, Alison, Casasús, Ana B, Duff, Jennifer, Mroczek, Magdalena, Specht, Sabine, Lek, Monkol, Ensini, Monica, MacArthur, Daniel G, MYO-SEQ consortium, Straub, Volker, Paquay, Stéphanie, Van den Bergh, Peter, Van Parys, Vinciane, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, UCL - (SLuc) Service de neurologie pédiatrique, Töpf, Ana, Johnson, Katherine, Bates, Adam, Phillips, Lauren, Chao, Katherine R, England, Eleina M, Laricchia, Kristen M, Mullen, Thomas, Valkanas, Elise, Xu, Liwen, Bertoli, Marta, Blain, Alison, Casasús, Ana B, Duff, Jennifer, Mroczek, Magdalena, Specht, Sabine, Lek, Monkol, Ensini, Monica, MacArthur, Daniel G, MYO-SEQ consortium, Straub, Volker, Paquay, Stéphanie, Van den Bergh, Peter, and Van Parys, Vinciane
Abstract: PURPOSE: Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. METHODS: Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. RESULTS: We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. CONCLUSION: Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes.
Published: 2020

35. Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy

Author: Bryen, Samantha J, Ewans, Lisa J, Pinner, Jason, MacLennan, Suzanna C, Donkervoort, Sandra, Castro, Diana, Töpf, Ana, O'Grady, Gina, Cummings, Beryl, Chao, Katherine R, Weisburd, Ben, Francioli, Laurent, Faiz, Fathimath, Bournazos, Adam M, Hu, Ying, Grosmann, Carla, Malicki, Denise M, Doyle, Helen, Witting, Nanna, Vissing, John, Claeys, Kristl G, Urankar, Kathryn, Beleza-Meireles, Ana, Baptista, Julia, Ellard, Sian, Savarese, Marco, Johari, Mridul, Vihola, Anna, Udd, Bjarne, Majumdar, Anirban, Straub, Volker, Bönnemann, Carsten G, MacArthur, Daniel G, Davis, Mark R, Cooper, Sandra T, Bryen, Samantha J, Ewans, Lisa J, Pinner, Jason, MacLennan, Suzanna C, Donkervoort, Sandra, Castro, Diana, Töpf, Ana, O'Grady, Gina, Cummings, Beryl, Chao, Katherine R, Weisburd, Ben, Francioli, Laurent, Faiz, Fathimath, Bournazos, Adam M, Hu, Ying, Grosmann, Carla, Malicki, Denise M, Doyle, Helen, Witting, Nanna, Vissing, John, Claeys, Kristl G, Urankar, Kathryn, Beleza-Meireles, Ana, Baptista, Julia, Ellard, Sian, Savarese, Marco, Johari, Mridul, Vihola, Anna, Udd, Bjarne, Majumdar, Anirban, Straub, Volker, Bönnemann, Carsten G, MacArthur, Daniel G, Davis, Mark R, and Cooper, Sandra T
Abstract: We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (NM_001267550.1:c.39974-11T>G), inherited in trans with a second pathogenic TTN variant. Muscle-derived RNA studies of three individuals confirmed mis-splicing induced by the c.39974-11T>G variant; in-frame exon 214 skipping or use of a cryptic 3' splice-site effecting a frameshift. Confounding interpretation of pathogenicity is the absence of exons 213-217 within the described skeletal muscle TTN N2A isoform. However, RNA-sequencing from 365 adult human gastrocnemius samples revealed that 56% specimens predominantly include exons 213-217 in TTN transcripts (inclusion rate ≥66%). Further, RNA-sequencing of five fetal muscle samples confirmed that 4/5 specimens predominantly include exons 213-217 (fifth sample inclusion rate 57%). Contractures improved significantly with age for four individuals, which may be linked to decreased expression of pathogenic fetal transcripts. Our study extends emerging evidence supporting a vital developmental role for TTN isoforms containing metatranscript-only exons.
Published: 2020

36. The Genetic Landscape of Diamond-Blackfan Anemia

Author: Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Ulirsch, Jacob C., Verboon, Jeffrey M., Kazerounian, Shideh, Guo, Michael H., Yuan, Daniel, Ludwig, Leif S., Handsaker, Robert E., Abdulhay, Nour J., Fiorini, Claudia, Genovese, Giulio, Lim, Elaine T., Cheng, Aaron, Cummings, Beryl B., Chao, Katherine R., Beggs, Alan H., Genetti, Casie A., Sieff, Colin A., Newburger, Peter E., Niewiadomska, Edyta, Matysiak, Michal, Vlachos, Adrianna, Lipton, Jeffrey M., Atsidaftos, Eva, Glader, Bertil, Narla, Anupama, Gleizes, Pierre-Emmanuel, O’Donohue, Marie-Françoise, Montel-Lehry, Nathalie, Amor, David J., McCarroll, Steven A, O’Donnell-Luria, Anne H., Gupta, Namrata, Gabriel, Stacey, MacArthur, Daniel G., Lander, Eric Steven, Lek, Monkol, Da Costa, Lydie, Nathan, David G., Korostelev, Andrei A., Do, Ron, Sankaran, Vijay G., Gazda, Hanna T., Diamond-Blackfan Anemia Cohort, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Ulirsch, Jacob C., Verboon, Jeffrey M., Kazerounian, Shideh, Guo, Michael H., Yuan, Daniel, Ludwig, Leif S., Handsaker, Robert E., Abdulhay, Nour J., Fiorini, Claudia, Genovese, Giulio, Lim, Elaine T., Cheng, Aaron, Cummings, Beryl B., Chao, Katherine R., Beggs, Alan H., Genetti, Casie A., Sieff, Colin A., Newburger, Peter E., Niewiadomska, Edyta, Matysiak, Michal, Vlachos, Adrianna, Lipton, Jeffrey M., Atsidaftos, Eva, Glader, Bertil, Narla, Anupama, Gleizes, Pierre-Emmanuel, O’Donohue, Marie-Françoise, Montel-Lehry, Nathalie, Amor, David J., McCarroll, Steven A, O’Donnell-Luria, Anne H., Gupta, Namrata, Gabriel, Stacey, MacArthur, Daniel G., Lander, Eric Steven, Lek, Monkol, Da Costa, Lydie, Nathan, David G., Korostelev, Andrei A., Do, Ron, Sankaran, Vijay G., Gazda, Hanna T., and Diamond-Blackfan Anemia Cohort
Abstract: Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole-exome sequencing (WES). We identified relevant rare and predicted damaging mutations for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and located in 1 of 19 previously reported ribosomal protein (RP)-encoding genes. Using exon coverage estimates, we identified and validated 31 deletions in RP genes. We also observed an enrichment for extended splice site mutations and validated their diverse effects using RNA sequencing in cell lines obtained from individuals with DBA. Leveraging the size of our cohort, we observed robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. We further identified rare mutations in seven previously unreported RP genes that may cause DBA, as well as several distinct disorders that appear to phenocopy DBA, including nine individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain >5% of DBA-affected case subjects. Overall, this report should inform not only clinical practice for DBA-affected individuals, but also the design and analysis of rare variant studies for heterogeneous Mendelian disorders.
Published: 2020

37. Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores

Author: Donkervoort, Sandra, primary, Kutzner, Carl E., additional, Hu, Ying, additional, Lornage, Xavière, additional, Rendu, John, additional, Stojkovic, Tanya, additional, Baets, Jonathan, additional, Neuhaus, Sarah B., additional, Tanboon, Jantima, additional, Maroofian, Reza, additional, Bolduc, Véronique, additional, Mroczek, Magdalena, additional, Conijn, Stefan, additional, Kuntz, Nancy L., additional, Töpf, Ana, additional, Monges, Soledad, additional, Lubieniecki, Fabiana, additional, McCarty, Riley M., additional, Chao, Katherine R., additional, Governali, Serena, additional, Böhm, Johann, additional, Boonyapisit, Kanokwan, additional, Malfatti, Edoardo, additional, Sangruchi, Tumtip, additional, Horkayne-Szakaly, Iren, additional, Hedberg-Oldfors, Carola, additional, Efthymiou, Stephanie, additional, Noguchi, Satoru, additional, Djeddi, Sarah, additional, Iida, Aritoshi, additional, di Rosa, Gabriella, additional, Fiorillo, Chiara, additional, Salpietro, Vincenzo, additional, Darin, Niklas, additional, Fauré, Julien, additional, Houlden, Henry, additional, Oldfors, Anders, additional, Nishino, Ichizo, additional, de Ridder, Willem, additional, Straub, Volker, additional, Pokrzywa, Wojciech, additional, Laporte, Jocelyn, additional, Foley, A. Reghan, additional, Romero, Norma B., additional, Ottenheijm, Coen, additional, Hoppe, Thorsten, additional, and Bönnemann, Carsten G., additional
Published: 2020
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38. Exome sequencing identifies novel missense and deletion variants inRTN4IP1associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis

Author: D'Gama, Alissa M., primary, England, Eleina, additional, Madden, Jill A., additional, Shi, Jiahai, additional, Chao, Katherine R., additional, Wojcik, Monica H., additional, Torres, Alcy R., additional, Tan, Wen‐Hann, additional, Berry, Gerard T., additional, Prabhu, Sanjay P., additional, and Agrawal, Pankaj B., additional
Published: 2020
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39. Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Author: Töpf, Ana, primary, Johnson, Katherine, additional, Bates, Adam, additional, Phillips, Lauren, additional, Chao, Katherine R., additional, England, Eleina M., additional, Laricchia, Kristen M., additional, Mullen, Thomas, additional, Valkanas, Elise, additional, Xu, Liwen, additional, Bertoli, Marta, additional, Blain, Alison, additional, Casasús, Ana B., additional, Duff, Jennifer, additional, Mroczek, Magdalena, additional, Specht, Sabine, additional, Lek, Monkol, additional, Ensini, Monica, additional, MacArthur, Daniel G., additional, Akay, Ela, additional, Alonso-Pérez, Jorge, additional, Baets, Jonathan, additional, Barisic, Nina, additional, Bastian, Alexandra, additional, Borell, Sabine, additional, Chamova, Teodora, additional, Claeys, Kristl, additional, Colomer, Jaume, additional, Coppens, Sandra, additional, Deconinck, Nicolas, additional, de Ridder, Willem, additional, Díaz-Manera, Jordi, additional, Domínguez-González, Cristina, additional, Duncan, Alexis, additional, Durmus, Hacer, additional, Fahmy, Nagia A., additional, Farrugia, Maria Elena, additional, Fernández-Torrón, Roberto, additional, Gonzalez-Quereda, Lidia, additional, Haberlova, Jana, additional, von der Hagen, Maja, additional, Hahn, Andreas, additional, Jakovčević, Antonia, additional, Jerico Pascual, Ivonne, additional, Kapetanovic, Solange, additional, Kenina, Viktorija, additional, Kirschner, Janbernd, additional, Klein, Andrea, additional, Kölbel, Heike, additional, Kostera-Pruszczyk, Anna, additional, Kulshrestha, Richa, additional, Lähdetie, Jaana, additional, Layegh, Mahsa, additional, Longman, Cheryl, additional, López de Munain, Adolfo, additional, Loscher, Wolfgang, additional, Lusakowska, Anna, additional, Maddison, Paul, additional, Magot, Armelle, additional, Majumdar, Anirban, additional, Martí, Pilar, additional, Martínez Arroyo, Amaia, additional, Mazanec, Radim, additional, Mercier, Sandra, additional, Mongini, Tiziana, additional, Muelas, Nuria, additional, Nascimento, Andrés, additional, Nafissi, Shahriar, additional, Omidi, Shirin, additional, Ortez, Carlos, additional, Paquay, Stéphanie, additional, Pereon, Yann, additional, Perić, Stojan, additional, Ponzalino, Valentina, additional, Rakočević Stojanović, Vidosava, additional, Remiche, Gauthier, additional, Rodríguez Sainz, Aida, additional, Rudnik, Sabine, additional, Sanchez Albisua, Iciar, additional, Santos, Manuela, additional, Schara, Ulrike, additional, Shatillo, Andriy, additional, Sertić, Jadranka, additional, Stephani, Ulrich, additional, Strang-Karlsson, Sonja, additional, Sznajer, Yves, additional, Tanev, Ani, additional, Tournev, Ivailo, additional, Van den Bergh, Peter, additional, Van Parijs, Vinciane, additional, Vílchez, Juan, additional, Vill, Katharina, additional, Vissing, John, additional, Wallgren-Pettersson, Carina, additional, Wanschitz, Julia, additional, Willis, Tracey, additional, Witting, Nanna, additional, Zulaica, Miren, additional, and Straub, Volker, additional
Published: 2020
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40. Biallelic loss of function variants inSYT2cause a treatable congenital onset presynaptic myasthenic syndrome

Author: Donkervoort, Sandra, primary, Mohassel, Payam, additional, Laugwitz, Lucia, additional, Zaki, Maha S., additional, Kamsteeg, Erik‐Jan, additional, Maroofian, Reza, additional, Chao, Katherine R., additional, Verschuuren‐Bemelmans, Corien C., additional, Horber, Veronka, additional, Fock, Annemarie J. M., additional, McCarty, Riley M., additional, Jain, Minal S., additional, Biancavilla, Victoria, additional, McMacken, Grace, additional, Nalls, Matthew, additional, Voermans, Nicol C., additional, Elbendary, Hasnaa M., additional, Snyder, Molly, additional, Cai, Chunyu, additional, Lehky, Tanya J., additional, Stanley, Valentina, additional, Iannaccone, Susan T., additional, Foley, A. Reghan, additional, Lochmüller, Hanns, additional, Gleeson, Joseph, additional, Houlden, Henry, additional, Haack, Tobias B., additional, Horvath, Rita, additional, and Bönnemann, Carsten G., additional
Published: 2020
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41. Expanding the phenotypic spectrum in RDH12-associated retinal disease

Author: Scott, Hilary A., primary, Place, Emily M., additional, Ferenchak, Kevin, additional, Zampaglione, Erin, additional, Wagner, Naomi E., additional, Chao, Katherine R., additional, DiTroia, Stephanie P., additional, Navarro-Gomez, Daniel, additional, Mukai, Shizuo, additional, Huckfeldt, Rachel M., additional, Pierce, Eric A., additional, and Bujakowska, Kinga M., additional
Published: 2020
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42. Recurrent TTN metatranscript‐only c.39974–11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy

Author: Bryen, Samantha J., primary, Ewans, Lisa J., additional, Pinner, Jason, additional, MacLennan, Suzanna C., additional, Donkervoort, Sandra, additional, Castro, Diana, additional, Töpf, Ana, additional, O'Grady, Gina, additional, Cummings, Beryl, additional, Chao, Katherine R., additional, Weisburd, Ben, additional, Francioli, Laurent, additional, Faiz, Fathimath, additional, Bournazos, Adam M., additional, Hu, Ying, additional, Grosmann, Carla, additional, Malicki, Denise M., additional, Doyle, Helen, additional, Witting, Nanna, additional, Vissing, John, additional, Claeys, Kristl G., additional, Urankar, Kathryn, additional, Beleza‐Meireles, Ana, additional, Baptista, Julia, additional, Ellard, Sian, additional, Savarese, Marco, additional, Johari, Mridul, additional, Vihola, Anna, additional, Udd, Bjarne, additional, Majumdar, Anirban, additional, Straub, Volker, additional, Bönnemann, Carsten G., additional, MacArthur, Daniel G., additional, Davis, Mark R., additional, and Cooper, Sandra T., additional
Published: 2019
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43. A hidden structural variation in a known IRD gene: a cautionary tale of two new disease candidate genes.

Author: Scott, Hilary A., Larson, Anna, Rong, Shi Song, Mehrotra, Sudeep, Butcher, Rossano, Chao, Katherine R., Wiggs, Janey L., Place, Emily M., Pierce, Eric A., and Bujakowska, Kinga M.
Subjects: DYSTROPHY, CELL lines, EXOMES, BIOINFORMATICS, DNA sequencing
Abstract: Rod-cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1 in 3500 people. More than 270 genes are known to be implicated in the inherited retinal degenerations (IRDs), yet genetic diagnosis for ~30% of IRD of patients remains elusive despite advances in sequencing technologies. The goal of this study was to determine the genetic causality in a family with RCD. Family members were given a full ophthalmic exam at the Retinal Service at Massachusetts Eye and Ear and consented to genetic testing. Whole-exome sequencing (WES) was performed and variants of interest were Sanger-validated. Functional assays were conducted in zebrafish along with splicing assays in relevant cell lines to determine the impact on retinal function. WES identified variants in two potential candidate genes that segregated with disease: GNL3 (G Protein Nucleolar 3) c.1187 +3A >C and c.1568-8C >A; and PDE4DIP (Phosphodiester 4D Interacting Protein) c.3868G >A (p.Glu1290Lys) and c.4603G >A (p.Ala1535Thr). Both genes were promising candidates based on their retinal involvement (development and interactions with IRD-associated proteins); however, the functional assays did not validate either gene. Subsequent WES reanalysis with an updated bioinformatics pipeline and widened search parameters led to the detection of a 94-bp duplication in PRPF31 (premRNA Processing Factor 31) c.73_266dup (p.Asp56GlyfsTer33) as the causal variant. Our study demonstrates the importance of thorough functional characterization of new disease candidate genes and the value of reanalyzing next-generation sequencing sequence data, which in our case led to identification of a hidden pathogenic variant in a known IRD gene. [ABSTRACT FROM AUTHOR]
Published: 2022
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44. The Genetic Landscape of Diamond-Blackfan Anemia

Author: Ulirsch, Jacob C., primary, Verboon, Jeffrey M., additional, Kazerounian, Shideh, additional, Guo, Michael H., additional, Yuan, Daniel, additional, Ludwig, Leif S., additional, Handsaker, Robert E., additional, Abdulhay, Nour J., additional, Fiorini, Claudia, additional, Genovese, Giulio, additional, Lim, Elaine T., additional, Cheng, Aaron, additional, Cummings, Beryl B., additional, Chao, Katherine R., additional, Beggs, Alan H., additional, Genetti, Casie A., additional, Sieff, Colin A., additional, Newburger, Peter E., additional, Niewiadomska, Edyta, additional, Matysiak, Michal, additional, Vlachos, Adrianna, additional, Lipton, Jeffrey M., additional, Atsidaftos, Eva, additional, Glader, Bertil, additional, Narla, Anupama, additional, Gleizes, Pierre-Emmanuel, additional, O’Donohue, Marie-Françoise, additional, Montel-Lehry, Nathalie, additional, Amor, David J., additional, McCarroll, Steven A., additional, O’Donnell-Luria, Anne H., additional, Gupta, Namrata, additional, Gabriel, Stacey B., additional, MacArthur, Daniel G., additional, Lander, Eric S., additional, Lek, Monkol, additional, Da Costa, Lydie, additional, Nathan, David G., additional, Korostelev, Andrei A., additional, Do, Ron, additional, Sankaran, Vijay G., additional, and Gazda, Hanna T., additional
Published: 2019
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45. ACTN2 mutations cause “Multiple structured Core Disease” (MsCD)

Author: Lornage, Xavière, primary, Romero, Norma B., additional, Grosgogeat, Claire A., additional, Malfatti, Edoardo, additional, Donkervoort, Sandra, additional, Marchetti, Michael M., additional, Neuhaus, Sarah B., additional, Foley, A. Reghan, additional, Labasse, Clémence, additional, Schneider, Raphaël, additional, Carlier, Robert Y., additional, Chao, Katherine R., additional, Medne, Livija, additional, Deleuze, Jean-François, additional, Orlikowski, David, additional, Bönnemann, Carsten G., additional, Gupta, Vandana A., additional, Fardeau, Michel, additional, Böhm, Johann, additional, and Laporte, Jocelyn, additional
Published: 2019
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46. MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance

Author: Dobyns, William B., primary, Aldinger, Kimberly A., additional, Ishak, Gisele E., additional, Mirzaa, Ghayda M., additional, Timms, Andrew E., additional, Grout, Megan E., additional, Dremmen, Marjolein H.G., additional, Schot, Rachel, additional, Vandervore, Laura, additional, van Slegtenhorst, Marjon A., additional, Wilke, Martina, additional, Kasteleijn, Esmee, additional, Lee, Arthur S., additional, Barry, Brenda J., additional, Chao, Katherine R., additional, Szczałuba, Krzysztof, additional, Kobori, Joyce, additional, Hanson-Kahn, Andrea, additional, Bernstein, Jonathan A., additional, Carr, Lucinda, additional, D’Arco, Felice, additional, Miyana, Kaori, additional, Okazaki, Tetsuya, additional, Saito, Yoshiaki, additional, Sasaki, Masayuki, additional, Das, Soma, additional, Wheeler, Marsha M., additional, Bamshad, Michael J., additional, Nickerson, Deborah A., additional, Engle, Elizabeth C., additional, Verheijen, Frans W., additional, Doherty, Dan, additional, and Mancini, Grazia M.S., additional
Published: 2018
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47. The Genetic Landscape of Diamond-Blackfan Anemia

Author: Ulirsch, Jacob C., primary, Verboon, Jeffrey M., additional, Kazerounian, Shideh, additional, Guo, Michael H., additional, Yuan, Daniel, additional, Ludwig, Leif S., additional, Handsaker, Robert E., additional, Abdulhay, Nour J., additional, Fiorini, Claudia, additional, Genovese, Giulio, additional, Lim, Elaine T., additional, Cheng, Aaron, additional, Cummings, Beryl B., additional, Chao, Katherine R., additional, Beggs, Alan H., additional, Genetti, Casie A., additional, Sieff, Colin A., additional, Newburger, Peter E., additional, Niewiadomska, Edyta, additional, Matysiak, Michal, additional, Vlachos, Adrianna, additional, Lipton, Jeffrey M., additional, Atsidaftos, Eva, additional, Glader, Bertil, additional, Narla, Anupama, additional, Gleizes, Pierre-Emmanuel, additional, O’Donohue, Marie-Françoise, additional, Montel-Lehry, Nathalie, additional, Amor, David J., additional, McCarroll, Steven A., additional, O’Donnell-Luria, Anne H., additional, Gupta, Namrata, additional, Gabriel, Stacey B., additional, MacArthur, Daniel G., additional, Lander, Eric S., additional, Lek, Monkol, additional, Da Costa, Lydie, additional, Nathan, David G., additional, Korostelev, Andrei A., additional, Do, Ron, additional, Sankaran, Vijay G., additional, and Gazda, Hanna T., additional
Published: 2018
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48. Exome sequencing identifies novel missense and deletion variants in RTN4IP1 associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis.

Author: D'Gama, Alissa M., England, Eleina, Madden, Jill A., Shi, Jiahai, Chao, Katherine R., Wojcik, Monica H., Torres, Alcy R., Tan, Wen‐Hann, Berry, Gerard T., Prabhu, Sanjay P., and Agrawal, Pankaj B.
Abstract: Inherited optic neuropathies (IONs) are neurodegenerative disorders characterized by optic atrophy with or without extraocular manifestations. Optic atrophy‐10 (OPA10) is an autosomal recessive ION recently reported to be caused by mutations in RTN4IP1, which encodes reticulon 4 interacting protein 1 (RTN4IP1), a mitochondrial ubiquinol oxydo‐reductase. Here we report novel compound heterozygous mutations in RTN4IP1 in a male proband with developmental delay, epilepsy, optic atrophy, ataxia, and choreoathetosis. Workup was notable for transiently elevated lactate and lactate‐to‐pyruvate ratio, brain magnetic resonance imaging with optic atrophy and T2 signal abnormalities, and a nondiagnostic initial genetic workup, including chromosomal microarray and mitochondrial panel testing. Exome sequencing identified a paternally inherited missense variant (c.263T>G, p.Val88Gly) predicted to be deleterious and a maternally inherited deletion encompassing RTN4IP1. To our knowledge, this is the first report of a non‐single nucleotide pathogenic variant associated with OPA10. This case highlights the expanding phenotypic spectrum of OPA10, the association between "syndromic" cases and severe RTN4IP1 mutations, and the importance of nonbiased genetic testing, such as ES, to analyze multiple genes and variants types, in patients suspected of having genetic disease. [ABSTRACT FROM AUTHOR]
Published: 2021
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49. Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome.

Author: Donkervoort, Sandra, Mohassel, Payam, Laugwitz, Lucia, Zaki, Maha S., Kamsteeg, Erik‐Jan, Maroofian, Reza, Chao, Katherine R., Verschuuren‐Bemelmans, Corien C., Horber, Veronka, Fock, Annemarie J. M., McCarty, Riley M., Jain, Minal S., Biancavilla, Victoria, McMacken, Grace, Nalls, Matthew, Voermans, Nicol C., Elbendary, Hasnaa M., Snyder, Molly, Cai, Chunyu, and Lehky, Tanya J.
Abstract: Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin‐2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant‐negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS‐disease gene and expands its clinical and genetic spectrum to include recessive loss‐of‐function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications. [ABSTRACT FROM AUTHOR]
Published: 2020
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50. Recurrent TTN metatranscript‐only c.39974–11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy.

Author: Bryen, Samantha J., Ewans, Lisa J., Pinner, Jason, MacLennan, Suzanna C., Donkervoort, Sandra, Castro, Diana, Töpf, Ana, O'Grady, Gina, Cummings, Beryl, Chao, Katherine R., Weisburd, Ben, Francioli, Laurent, Faiz, Fathimath, Bournazos, Adam M., Hu, Ying, Grosmann, Carla, Malicki, Denise M., Doyle, Helen, Witting, Nanna, and Vissing, John
Abstract: We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice‐site variant (NM_001267550.1:c.39974‐11T>G), inherited in trans with a second pathogenic TTN variant. Muscle‐derived RNA studies of three individuals confirmed mis‐splicing induced by the c.39974‐11T>G variant; in‐frame exon 214 skipping or use of a cryptic 3′ splice‐site effecting a frameshift. Confounding interpretation of pathogenicity is the absence of exons 213‐217 within the described skeletal muscle TTN N2A isoform. However, RNA‐sequencing from 365 adult human gastrocnemius samples revealed that 56% specimens predominantly include exons 213‐217 in TTN transcripts (inclusion rate ≥66%). Further, RNA‐sequencing of five fetal muscle samples confirmed that 4/5 specimens predominantly include exons 213‐217 (fifth sample inclusion rate 57%). Contractures improved significantly with age for four individuals, which may be linked to decreased expression of pathogenic fetal transcripts. Our study extends emerging evidence supporting a vital developmental role for TTN isoforms containing metatranscript‐only exons. [ABSTRACT FROM AUTHOR]
Published: 2020
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