384 results on '"Wakeling, Emma"'
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2. Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt
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Shepherdson, James L., Hutchison, Katie, Don, Dilan Wellalage, McGillivray, George, Choi, Tae-Ik, Allan, Carolyn A., Amor, David J., Banka, Siddharth, Basel, Donald G., Buch, Laura D., Carere, Deanna Alexis, Carroll, Renée, Clayton-Smith, Jill, Crawford, Ali, Dunø, Morten, Faivre, Laurence, Gilfillan, Christopher P., Gold, Nina B., Gripp, Karen W., Hobson, Emma, Holtz, Alexander M., Innes, A. Micheil, Isidor, Bertrand, Jackson, Adam, Katsonis, Panagiotis, Amel Riazat Kesh, Leila, Küry, Sébastien, Lecoquierre, François, Lockhart, Paul, Maraval, Julien, Matsumoto, Naomichi, McCarrier, Julie, McCarthy, Josephine, Miyake, Noriko, Moey, Lip Hen, Németh, Andrea H., Østergaard, Elsebet, Patel, Rushina, Pope, Kate, Posey, Jennifer E., Schnur, Rhonda E., Shaw, Marie, Stolerman, Elliot, Taylor, Julie P., Wadman, Erin, Wakeling, Emma, White, Susan M., Wong, Lawrence C., Lupski, James R., Lichtarge, Olivier, Corbett, Mark A., Gecz, Jozef, Nicolet, Charles M., Farnham, Peggy J., Kim, Cheol-Hee, and Shinawi, Marwan
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- 2024
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3. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections
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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.
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- 2024
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4. Clinical and molecular characterization of novel FARS2 variants causing neonatal mitochondrial disease
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Chen, Wenqian, Rehsi, Preeya, Thompson, Kyle, Yeo, Mildrid, Stals, Karen, He, Langping, Schimmel, Paul, Chrzanowska-Lightowlers, Zofia M.A., Wakeling, Emma, Taylor, Robert W., and Kuhle, Bernhard
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- 2023
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5. Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders
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Sanchis-Juan, Alba, Megy, Karyn, Stephens, Jonathan, Armirola Ricaurte, Camila, Dewhurst, Eleanor, Low, Kayyi, French, Courtney E., Grozeva, Detelina, Stirrups, Kathleen, Erwood, Marie, McTague, Amy, Penkett, Christopher J., Shamardina, Olga, Tuna, Salih, Daugherty, Louise C., Gleadall, Nicholas, Duarte, Sofia T., Hedrera-Fernández, Antonio, Vogt, Julie, Ambegaonkar, Gautam, Chitre, Manali, Josifova, Dragana, Kurian, Manju A., Parker, Alasdair, Rankin, Julia, Reid, Evan, Wakeling, Emma, Wassmer, Evangeline, Woods, C. Geoffrey, Raymond, F. Lucy, and Carss, Keren J.
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- 2023
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6. Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease
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Calame, Daniel G., Guo, Tianyu, Wang, Chen, Garrett, Lillian, Jolly, Angad, Dawood, Moez, Kurolap, Alina, Henig, Noa Zunz, Fatih, Jawid M., Herman, Isabella, Du, Haowei, Mitani, Tadahiro, Becker, Lore, Rathkolb, Birgit, Gerlini, Raffaele, Seisenberger, Claudia, Marschall, Susan, Hunter, Jill V., Gerard, Amanda, Heidlebaugh, Alexis, Challman, Thomas, Spillmann, Rebecca C., Jhangiani, Shalini N., Coban-Akdemir, Zeynep, Lalani, Seema, Liu, Lingxiao, Revah-Politi, Anya, Iglesias, Alejandro, Guzman, Edwin, Baugh, Evan, Boddaert, Nathalie, Rondeau, Sophie, Ormieres, Clothide, Barcia, Giulia, Tan, Queenie K.G., Thiffault, Isabelle, Pastinen, Tomi, Sheikh, Kazim, Biliciler, Suur, Mei, Davide, Melani, Federico, Shashi, Vandana, Yaron, Yuval, Steele, Mary, Wakeling, Emma, Østergaard, Elsebet, Nazaryan-Petersen, Lusine, Millan, Francisca, Santiago-Sim, Teresa, Thevenon, Julien, Bruel, Ange-Line, Thauvin-Robinet, Christel, Popp, Denny, Platzer, Konrad, Gawlinski, Pawel, Wiszniewski, Wojciech, Marafi, Dana, Pehlivan, Davut, Posey, Jennifer E., Gibbs, Richard A., Gailus-Durner, Valerie, Guerrini, Renzo, Fuchs, Helmut, Hrabě de Angelis, Martin, Hölter, Sabine M., Cheung, Hoi-Hung, Gu, Shen, and Lupski, James R.
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- 2023
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7. De novo PHF5A variants are associated with craniofacial abnormalities, developmental delay, and hypospadias
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Harms, Frederike L., Dingemans, Alexander J.M., Hempel, Maja, Pfundt, Rolph, Bierhals, Tatjana, Casar, Christian, Müller, Christian, Niermeijer, Jikke-Mien F., Fischer, Jan, Jahn, Arne, Hübner, Christoph, Majore, Silvia, Agolini, Emanuele, Novelli, Antonio, van der Smagt, Jasper, Ernst, Robert, van Binsbergen, Ellen, Mancini, Grazia M.S., van Slegtenhorst, Marjon, Barakat, Tahsin S., Wakeling, Emma L., Kamath, Arveen, Downie, Lilian, Pais, Lynn, White, Susan M., de Vries, Bert B.A., and Kutsche, Kerstin
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- 2023
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8. Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review
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Sabanathan, Saraswathy, Gulhane, Deepti, Mankad, Kshitij, Davison, James, Ong, Min Tsui, Phadke, Rahul, Robinson, Robert, Spiller, Michael, Wakeling, Emma, Ramdas, Sithara, Brady, Angela F, Balasubramanian, Meena, and Munot, Pinki
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- 2023
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9. Body Composition and Metabolism in Adults With Molecularly Confirmed Silver-Russell Syndrome.
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Lokulo-Sodipe, Oluwakemi, Inskip, Hazel M, Byrne, Christopher D, Child, Jenny, Wakeling, Emma L, Mackay, Deborah J G, Temple, I Karen, and Davies, Justin H
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BONE density ,BODY mass index ,LOW birth weight ,ADIPOSE tissues ,MEDIAN (Mathematics) - Abstract
Context Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long-term outcomes and adult body composition in SRS are limited. Objective To evaluate body composition and metabolic health in adults with SRS. Methods This was an observational study of 25 individuals with molecularly confirmed SRS, aged ≥ 18 years, from research facilities across the UK. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey [SWS]). Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured. Results Twenty-five adults with SRS were included (52% female). The median age was 32.9 years (range, 22.0 to 69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, P <.001). Fat mass index was similar (9.6 vs 7.8, P =.3). Lean mass percentage (51.8% vs 66.2%, P <.001) and lean mass index (13.5 kg/m
2 vs 17.3 kg/m2 , P <.001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, P <.001; all median values). Total cholesterol was ≥ 5 mmol/L in 52.0%. Triglyceride levels were ≥ 1.7 mmol/L in 20.8%. Fasting blood glucose levels were ≥ 6.1 mmol/L in 25.0%. Hypertension was present in 33.3%. Conclusion Adults with SRS have an unfavorable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2024
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10. Biallelic mutations in SUPV3L1 cause an inherited neurodevelopmental disorder with variable leukodystrophy due to aberrant mitochondrial double stranded RNA processing
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Green, Lydia, primary, Hamilton, Noémie, additional, Elpidorou, Marilena, additional, Maroofian, Reza, additional, Douglas, Andrew G.L., additional, Õunap, Katrin, additional, Rose, Ailsa M.S., additional, Harris, Erica L., additional, Elworthy, Stone, additional, Renshaw, Stephen A., additional, Low, Elizabeth C., additional, Dockrell, David H., additional, Tveten, Kristian, additional, Wells, Geoffrey, additional, Harris, Sarah A., additional, Al-Maawali, Almundher, additional, Al-Thihli, Khalid, additional, Al-Zuhaibi, Sana, additional, Futaisi, Amna Al, additional, Calame, Daniel, additional, Chinn, Ivan, additional, Fisher, Kristen S., additional, Sa, Mario, additional, Warren, Daniel, additional, Zamani, Mina, additional, Sadeghian, Saeid, additional, Azizimalamiri, Reza, additional, Galehdari, Hamid, additional, Shariati, Gholamreza, additional, Seifi, Tahere, additional, Zaki, Maha S., additional, Afzal, Erum, additional, Tarnopolsky, Mark A., additional, Brady, Lauren, additional, Zuchner, Stephan L., additional, Efthymiou, Stephanie, additional, Scardamaglia, Annarita, additional, Houlden, Henry, additional, Wakeling, Emma, additional, Prabhakar, Prab, additional, Roca-Bayerri, Carla, additional, Rice, Gillian I., additional, Prouteau, Clément, additional, Bris, Céline, additional, Tessarech, Marine, additional, Sandvig, Inger, additional, Sheridan, Eamonn G., additional, Johnson, Colin A., additional, Livingston, John H., additional, Crow, Yanick J., additional, and Poulter, James A., additional
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- 2024
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11. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease
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Carss, Keren J, Arno, Gavin, Erwood, Marie, Stephens, Jonathan, Sanchis-Juan, Alba, Hull, Sarah, Megy, Karyn, Grozeva, Detelina, Dewhurst, Eleanor, Malka, Samantha, Plagnol, Vincent, Penkett, Christopher, Stirrups, Kathleen, Rizzo, Roberta, Wright, Genevieve, Josifova, Dragana, Bitner-Glindzicz, Maria, Scott, Richard H, Clement, Emma, Allen, Louise, Armstrong, Ruth, Brady, Angela F, Carmichael, Jenny, Chitre, Manali, Henderson, Robert HH, Hurst, Jane, MacLaren, Robert E, Murphy, Elaine, Paterson, Joan, Rosser, Elisabeth, Thompson, Dorothy A, Wakeling, Emma, Ouwehand, Willem H, Michaelides, Michel, Moore, Anthony T, Consortium, NIHR-BioResource Rare Diseases, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Church, Colin, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, Deshpande, Charu, Devlin, Lisa, Doffinger, Rainer, Dormand, Natalie, Drewe, Elizabeth, and Edgar, David
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Genetics ,Neurosciences ,Eye Disease and Disorders of Vision ,Human Genome ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Eye ,Good Health and Well Being ,Adaptor Proteins ,Signal Transducing ,Alleles ,Base Sequence ,Choroideremia ,DNA Mutational Analysis ,Ethnicity ,Exome ,Female ,Genes ,Recessive ,Genetic Variation ,Genome ,Human ,Humans ,Introns ,Male ,Mutation ,Rare Diseases ,Retinal Diseases ,NIHR-BioResource Rare Diseases Consortium ,copy-number variants ,rare sequence variant ,retinal dystrophy ,whole-genome sequence ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.
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- 2017
12. The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders
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Genetica Klinische Genetica, Child Health, MS Radiologie, Circulatory Health, MS Neonatologie, Sidpra, Jai, Sudhakar, Sniya, Biswas, Asthik, Massey, Flavia, Turchetti, Valentina, Lau, Tracy, Cook, Edward, Alvi, Javeria Raza, Elbendary, Hasnaa M, Jewell, Jerry L, Riva, Antonella, Orsini, Alessandro, Vignoli, Aglaia, Federico, Zara, Rosenblum, Jessica, Schoonjans, An-Sofie, de Wachter, Matthias, Delgado Alvarez, Ignacio, Felipe-Rucián, Ana, Haridy, Nourelhoda A, Haider, Shahzad, Zaman, Mashaya, Banu, Selina, Anwaar, Najwa, Rahman, Fatima, Maqbool, Shazia, Yadav, Rashmi, Salpietro, Vincenzo, Maroofian, Reza, Patel, Rajan, Radhakrishnan, Rupa, Prabhu, Sanjay P, Lichtenbelt, Klaske, Stewart, Helen, Murakami, Yoshiko, Löbel, Ulrike, D'Arco, Felice, Wakeling, Emma, Jones, Wendy, Hay, Eleanor, Bhate, Sanjay, Jacques, Thomas S, Mirsky, David M, Whitehead, Matthew T, Zaki, Maha S, Sultan, Tipu, Striano, Pasquale, Jansen, Anna C, Lequin, Maarten, de Vries, Linda S, Severino, Mariasavina, Edmondson, Andrew C, Menzies, Lara, Campeau, Philippe M, Houlden, Henry, McTague, Amy, Efthymiou, Stephanie, Mankad, Kshitij, Genetica Klinische Genetica, Child Health, MS Radiologie, Circulatory Health, MS Neonatologie, Sidpra, Jai, Sudhakar, Sniya, Biswas, Asthik, Massey, Flavia, Turchetti, Valentina, Lau, Tracy, Cook, Edward, Alvi, Javeria Raza, Elbendary, Hasnaa M, Jewell, Jerry L, Riva, Antonella, Orsini, Alessandro, Vignoli, Aglaia, Federico, Zara, Rosenblum, Jessica, Schoonjans, An-Sofie, de Wachter, Matthias, Delgado Alvarez, Ignacio, Felipe-Rucián, Ana, Haridy, Nourelhoda A, Haider, Shahzad, Zaman, Mashaya, Banu, Selina, Anwaar, Najwa, Rahman, Fatima, Maqbool, Shazia, Yadav, Rashmi, Salpietro, Vincenzo, Maroofian, Reza, Patel, Rajan, Radhakrishnan, Rupa, Prabhu, Sanjay P, Lichtenbelt, Klaske, Stewart, Helen, Murakami, Yoshiko, Löbel, Ulrike, D'Arco, Felice, Wakeling, Emma, Jones, Wendy, Hay, Eleanor, Bhate, Sanjay, Jacques, Thomas S, Mirsky, David M, Whitehead, Matthew T, Zaki, Maha S, Sultan, Tipu, Striano, Pasquale, Jansen, Anna C, Lequin, Maarten, de Vries, Linda S, Severino, Mariasavina, Edmondson, Andrew C, Menzies, Lara, Campeau, Philippe M, Houlden, Henry, McTague, Amy, Efthymiou, Stephanie, and Mankad, Kshitij
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- 2024
13. Novel antenatal presentation of cystic hygroma in a case of Koolen–de Vries syndrome
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Oakley-Hannibal, Elizabeth, Tyagi, Vipin, Das, Shyam, Wakeling, Emma, and Gardham, Alice
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- 2022
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14. Expanding the phenotypic spectrum of ALDH18A1-related autosomal recessive cutis laxa with a description of novel neuroradiological findings
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Pickwick, Charlotte, Callewaert, Bert, van Dijk, Fleur, Harris, Juliette, Wakeling, Emma, Hay, Eleanor, Yeo, Mildrid, Chakrapani, Anupam, Baptista, Julia, Moore, Sandra, Yoong, Michael, Chatterjee, Fiona, and Ghali, Neeti
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- 2021
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15. Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene
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Malbos, Marlène, primary, Wakeling, Emma, additional, Gautier, Thierry, additional, Boespflug‐Tanguy, Odile, additional, Busby, Louise, additional, Taylor‐Miller, Tashunka, additional, Dudoignon, Benjamin, additional, Bokov, Plamen, additional, Govin, Jérôme, additional, Grisval, Margot, additional, Rega, Adélaïde, additional, Mourot De Rougemont, Marie‐Gabrielle, additional, Aubriot‐Lorton, Marie‐Hélène, additional, Darmency, Véronique, additional, Bensignor, Candace, additional, Houzel, Anne, additional, Huet, Frédéric, additional, Denommé‐Pichon, Anne‐Sophie, additional, Delanne, Julian, additional, Tran Mau‐Them, Frédéric, additional, Bruel, Ange‐Line, additional, Safraou, Hana, additional, Nambot, Sophie, additional, Garde, Aurore, additional, Philippe, Christophe, additional, Duffourd, Yannis, additional, Vitobello, Antonio, additional, Faivre, Laurence, additional, and Thauvin‐Robinet, Christel, additional
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- 2024
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16. A clinical scoring system for congenital contractural arachnodactyly
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Meerschaut, Ilse, De Coninck, Shana, Steyaert, Wouter, Barnicoat, Angela, Bayat, Allan, Benedicenti, Francesco, Berland, Siren, Blair, Edward M., Breckpot, Jeroen, de Burca, Anna, Destrée, Anne, García-Miñaúr, Sixto, Green, Andrew J., Hanna, Bernadette C., Keymolen, Kathelijn, Koopmans, Marije, Lederer, Damien, Lees, Melissa, Longman, Cheryl, Lynch, Sally Ann, Male, Alison M., McKenzie, Fiona, Migeotte, Isabelle, Mihci, Ercan, Nur, Banu, Petit, Florence, Piard, Juliette, Plasschaert, Frank S., Rauch, Anita, Ribaï, Pascale, Pacheco, Iratxe Salcedo, Stanzial, Franco, Stolte-Dijkstra, Irene, Valenzuela, Irene, Varghese, Vinod, Vasudevan, Pradeep C., Wakeling, Emma, Wallgren-Pettersson, Carina, Coucke, Paul, De Paepe, Anne, De Wolf, Daniël, Symoens, Sofie, and Callewaert, Bert
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- 2020
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17. Expanding the allelic spectrum of ELOVL4‐related autosomal recessive neuro‐ichthyosis
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Alabdulrazzaq, Fatima, primary, Alanzi, Talal, additional, Al‐Balool, Haya H., additional, Gardham, Alice, additional, Wakeling, Emma, additional, Leitch, Harry G., additional, AlSayed, Moeenaldeen, additional, Abdulrahim, Maha, additional, Aladwani, Abdulaziz, additional, Romito, Antonio, additional, Kampe, Kapil, additional, Ferdinandusse, Sacha, additional, Aboelanine, Ashraf H., additional, Abdullah, Amira, additional, Alwadani, Amal, additional, Bastaki, Laila, additional, Vaz, Frédéric M., additional, Bertoli‐Avella, Aida M., additional, and Marafi, Dana, additional
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- 2023
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18. A novel autosomal recessive DEAF1 nonsense variant: expanding the clinical phenotype
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Andoni, Tala, Ellard, Sian, Kapadia, Jogesh, and Wakeling, Emma
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- 2020
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19. Genomic imprinting and Silver-Russell syndrome : candidate genes on chromosome 7
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Wakeling, Emma Louise
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572.8 ,SRS - Abstract
Silver-Russell syndrome (SRS) is characterised by intrauterine and postnatal growth retardation, triangular facies, fifth finger clinodactyly and lateral asymmetry. Maternal uniparental disomy of chromosome 7 (mUDP7) has been demonstrated in approximately 7% of patients. No consistently isodisomic regions have been found. It is likely, therefore, that one or more imprinted gene(s) on chromosome 7 are involved in SRS. Five candidate genes located on this chromosome have been studied. The human chromosomal region 7p11.2-13 is homologous to an imprinted region on mouse proximal chromosome 11. Maternal UPD for this region leads to mice with prenatal growth failure. Three growth-related genes, IGFBP1 and 3 (insulin-like growth factor binding proteins 1 and 3) and EGFR (epidermal growth factor receptor), lie within this region and have been proposed as candidates for SRS. The imprinting status of these genes was previously unknown. Their parental allele expression was therefore investigated in normal fetal tissues using transcribed polymorphisms. Biallelic expression of all three genes was observed. Expression of IGFBP3 and EGFR was also seen in cell lines from mUPD7 patients. Since no evidence for imprinting of these three genes was found, their involvement in SRS seems unlikely. Recently, MEST (mesoderm specific transcript) became the first imprinted gene to be identified on chromosome 7. Its possible role in SRS was investigated by studying allelic methylation patterns using methylation-specific PCR. Normal differential methylation of MEST was found in 46, non-UPD SRS patients. It is therefore unlikely that this gene plays a major role in SRS. Finally, the growth suppressing gene GRB10 (growth factor receptor binding protein 10) has also recently been proposed as a candidate for SRS. A de novo duplication of 7p11.2-p12, including GRBIO, was observed in one SRS proband, providing further support for a role for this gene in SRS. However, Southern blot hybridisation showed normal GRB10 dosage in 36 other, non-UPD patients. Further investigation into the potential role of GRB10 and/or other genes within the region 7p11.2-p12 is needed.
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- 1999
20. A three-generation family with metaphyseal dysplasia, maxillary hypoplasia and brachydactyly (MDMHB) due to intragenic RUNX2 duplication
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Al-Yassin, Amina, Calder, Alistair D., Harrison, Mike, Lester, Tracy, Lord, Helen, Oldridge, Michael, Watkins, Sophie, Keen, Richard, and Wakeling, Emma L.
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- 2018
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21. BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome
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Olley, Gabrielle, Ansari, Morad, Bengani, Hemant, Grimes, Graeme R., Rhodes, James, von Kriegsheim, Alex, Blatnik, Ana, Stewart, Fiona J., Wakeling, Emma, Carroll, Nicola, Ross, Alison, Park, Soo-Mi, Deciphering Developmental Disorders Study, Bickmore, Wendy A., Pradeepa, Madapura M., and FitzPatrick, David R.
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- 2018
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22. HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients
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Moortgat, Stéphanie, Berland, Siren, Aukrust, Ingvild, Maystadt, Isabelle, Baker, Laura, Benoit, Valerie, Caro-Llopis, Alfonso, Cooper, Nicola S., Debray, François-Guillaume, Faivre, Laurence, Gardeitchik, Thatjana, Haukanes, Bjørn I., Houge, Gunnar, Kivuva, Emma, Martinez, Francisco, Mehta, Sarju G., Nassogne, Marie-Cécile, Powell-Hamilton, Nina, Pfundt, Rolph, Rosello, Monica, Prescott, Trine, Vasudevan, Pradeep, van Loon, Barbara, Verellen-Dumoulin, Christine, Verloes, Alain, Lippe, Charlotte von der, Wakeling, Emma, Wilkie, Andrew O. M., Wilson, Louise, Yuen, Amy, Study, DDD, Low, Karen J., and Newbury-Ecob, Ruth A.
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- 2018
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23. jamaneurology_morton_2022_rv_220001_1646244188.29201.pdf
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Morton, Sarah U, Christodoulou, John, Costain, Gregory, Muntoni, Francesco, Wakeling, Emma, Wojcik, Monica, French, Courtney E., Szuto, Anna, Dowling, James J., D. Cohn, Ronald, Raymond, F. Lucy, T. Darras, Basil, A. Williams, David, Lunke, Sebastian, Stark, Zornitza, Rowitch, David H., and B. Agrawal, Pankaj
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Infant and child health ,Neonatology - Abstract
IMPORTANCE Infants with hypotonia can present with a variety of potentially severe clinical signs and symptoms and often require invasive testing and multiple procedures. The wide range of clinical presentations and potential etiologies leaves diagnosis and prognosis uncertain, underscoring the need for rapid elucidation of the underlying genetic cause of disease. OBSERVATIONS The clinical application of exome sequencing or genome sequencing has dramatically improved the timely yield of diagnostic testing for neonatal hypotonia, with diagnostic rates of greater than 50% in academic neonatal intensive care units (NICUs) across Australia, Canada, the UK, and the US, which compose the International Precision Child Health Partnership (IPCHiP). A total of 74% (17 of 23) of patients had a change in clinical care in response to genetic diagnosis, including 2 patients who received targeted therapy. This narrative review discusses the common causes of neonatal hypotonia, the relative benefits and limitations of available testing modalities used in NICUs, and hypotonia management recommendations. CONCLUSIONS AND RELEVANCE This narrative review summarizes the causes of neonatal hypotonia and the benefits of prompt genetic diagnosis, including improved prognostication and identification of targeted treatments which can improve the short-term and long-term outcomes. Institutional resources can vary among different NICUs; as a result, consideration should be given to rule out a small number of relatively unique conditions for which rapid targeted genetic testing is available. Nevertheless, the consensus recommendation is to use rapid genome or exome sequencing as a first-line testing option for NICU patients with unexplained hypotonia. As part of the IPCHiP, this diagnostic experience will be collected in a central database with the goal of advancing knowledge of neonatal hypotonia and improving evidence-based practice.
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- 2023
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24. Resistance to thyroid hormone alpha: molecular, biochemical and physiological approach to diagnosis and therapy
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Agostini, Maura, primary, Pietzner, Maik, additional, Marelli, Federica, additional, Prapa, Matina, additional, Moran, Carla, additional, Edward, Visser W., additional, Brown, Dave, additional, Thomas, Ellen, additional, Schoenmakers, Erik, additional, Romartinez-Alonso, Beatriz, additional, Scheuplein, Rabea, additional, Tylki-Szymanska, Anna, additional, Lyons, Greta, additional, Watson, Laura, additional, Rajanayagam, Odelia, additional, Schwedhelm, Edzard, additional, F., Hartmann Michaela, additional, Wudy, Stefan, additional, Probst, Maiken, additional, MacDonald, Stephen, additional, Thomas, William, additional, Arlt, Wiebke, additional, Volker, Uwe, additional, M., Main Katharina, additional, Feldt-Rasmussen, Ulla, additional, T., Dattani Mehul, additional, Koren, Dahll Louise, additional, Demir, Korcan, additional, Kara, Cengiz, additional, Kirbiyik, Ozgur, additional, Mammadova, Jamala, additional, Cayır, Atilla, additional, Yarali, Oguzhan, additional, Phan-Hug, Franziska, additional, Sakremath, Rajesh, additional, Mohamed, Zainaba, additional, Shinawi, Marwan, additional, Gill, Harpreet, additional, pacaud, Daniele, additional, Perrier, Renee, additional, Poke, Gemma, additional, Hunter, Wendy, additional, Douzgou, Sofia, additional, Wakeling, Emma, additional, Gardham, Alice, additional, Lim, Derek, additional, Shears, Deborah, additional, Freel, Marie, additional, Omladic, Jasna, additional, Tansek, Mojca, additional, Writzl, Karin, additional, Farooqi, Sadaf, additional, Kopp, Peter, additional, Schwabe, John, additional, Persani, Luca, additional, and Chatterjee, Krishna, additional
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- 2022
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25. Heterozygous mutations affecting the protein kinase domain of CDK13 cause a syndromic form of developmental delay and intellectual disability
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Hamilton, Mark J, Caswell, Richard C, Canham, Natalie, Cole, Trevor, Firth, Helen V, Foulds, Nicola, Heimdal, Ketil, Hobson, Emma, Houge, Gunnar, Joss, Shelagh, Kumar, Dhavendra, Lampe, Anne Katrin, Maystadt, Isabelle, McKay, Victoria, Metcalfe, Kay, Newbury-Ecob, Ruth, Park, Soo-Mi, Robert, Leema, Rustad, Cecilie F, Wakeling, Emma, Wilkie, Andrew O M, Study, The Deciphering Developmental Disorders, Twigg, Stephen R F, and Suri, Mohnish
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- 2018
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26. Diagnosis of lethal or prenatal‐onset autosomal recessive disorders by parental exome sequencing
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Stals, Karen L., Wakeling, Matthew, Baptista, Júlia, Caswell, Richard, Parrish, Andrew, Rankin, Julia, Tysoe, Carolyn, Jones, Garan, Gunning, Adam C., Lango Allen, Hana, Bradley, Lisa, Brady, Angela F., Carley, Helena, Carmichael, Jenny, Castle, Bruce, Cilliers, Deirdre, Cox, Helen, Deshpande, Charu, Dixit, Abhijit, Eason, Jacqueline, Elmslie, Frances, Fry, Andrew E., Fryer, Alan, Holder, Muriel, Homfray, Tessa, Kivuva, Emma, McKay, Victoria, Newbury‐Ecob, Ruth, Parker, Michael, Savarirayan, Ravi, Searle, Claire, Shannon, Nora, Shears, Deborah, Smithson, Sarah, Thomas, Ellen, Turnpenny, Peter D., Varghese, Vinod, Vasudevan, Pradeep, Wakeling, Emma, Baple, Emma L., and Ellard, Sian
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- 2018
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27. Craniosynostosis, inner ear, and renal anomalies in a child with complete loss of SPRY1 (sprouty homolog 1) function.
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Tooze, Rebecca S., Calpena, Eduardo, Twigg, Stephen R. F., D'Arco, Felice, Wakeling, Emma L., and Wilkie, Andrew O. M.
- Abstract
Introduction SPRY1 encodes protein sprouty homolog 1 (Spry-1), a negative regulator of receptor tyrosine kinase signalling. Null mutant mice display kidney/urinary tract abnormalities and altered size of the skull; complete loss-of-function of Spry-1 in humans has not been reported. Methods Analysis of whole-genome sequencing data from individuals with craniosynostosis enrolled in the 100,000 Genomes Project identified a likely pathogenic variant within SPRY1. Reverse-transcriptase PCR and western blot analysis were used to investigate the effect of the variant on SPRY1 mRNA and protein, in lymphoblastoid cell lines from the patient and both parents. Results A nonsense variant in SPRY1, encoding p.(Leu27*), was confirmed to be heterozygous in the unaffected parents and homozygous in the child. The child's phenotype, which included sagittal craniosynostosis, subcutaneous cystic lesions overlying the lambdoid sutures, hearing loss associated with bilateral cochlear and vestibular dysplasia and a unilateral renal cyst, overlapped the features reported in Spry1-/- null mice. Functional studies supported escape from nonsense-mediated decay, but western blot analysis demonstrated complete absence of full-length protein in the affected child and a marked reduction in both parents. Conclusion This is the first report of complete loss of Spry-1 function in humans, associated with abnormalities of the cranial sutures, inner ear, and kidneys. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Combined novel homozygous variants in both SGPL1 and STAT1 presenting with severe combined immune deficiency: case report and literature review.
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Roa-Bautista, Adriel, Sohail, Mahreen, Wakeling, Emma, Gilmour, Kimberly C., Davis, Mark, Gait, Anthony, Lucchini, Giovanna, Cox, David, Elfeky, Reem, and Kusters, Maaike
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LITERATURE reviews ,STAT proteins ,ICHTHYOSIS ,SEVERE combined immunodeficiency ,HEMATOPOIETIC stem cell transplantation ,IMMUNODEFICIENCY ,ADRENAL insufficiency - Abstract
Background: Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is associated with biallelic variants in SGPL1, comprising a multisystemic disease characterized by steroid resistant nephrotic syndrome, primary adrenal insufficiency, neurological problems, skin abnormalities and immunodeficiency in described cases. Signal transducer and activator of transcription 1 (STAT1) plays an important role in orchestrating an appropriate immune response through JAK-STAT pathway. Biallelic STAT1 loss of function (LOF) variants lead to STAT1 deficiency with a severe phenotype of immunodeficiency with increased frequency of infections and poor outcome if untreated. Case presentation: We report novel homozygous SGPL1 and STAT1 variants in a newborn of Gambian ethnicity with clinical features of SPLIS and severe combined immunodeficiency. The patient presented early in life with nephrotic syndrome, severe respiratory infection requiring ventilation, ichthyosis, and hearing loss, with T-cell lymphopenia. The combination of these two conditions led to severe combined immunodeficiency with inability to clear respiratory tract infections of viral, fungal, and bacterial nature, as well as severe nephrotic syndrome. The child sadly died at 6 weeks of age despite targeted treatments. Conclusion: We report the finding of two novel, homozygous variants in SGPL1 and STAT1 in a patient with a severe clinical phenotype and fatal outcome early in life. This case highlights the importance of completing the primary immunodeficiency genetic panel in full to avoid missing a second diagnosis in other patients presenting with similar severe clinical phenotype early in life. For SPLIS no curative treatment is available and more research is needed to investigate different treatment modalities. Hematopoietic stem cell transplantation (HSCT) shows promising results in patients with autosomal recessive STAT1 deficiency. For this patient's family, identification of the dual diagnosis has important implications for future family planning. In addition, future siblings with the familial STAT1 variant can be offered curative treatment with HSCT. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Emerging phenotypes linked to variants in SAMD9 and MIRAGE syndrome
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Suntharalingham, Jenifer P., primary, Ishida, Miho, additional, Del Valle, Ignacio, additional, Stalman, Susanne E., additional, Solanky, Nita, additional, Wakeling, Emma, additional, Moore, Gudrun E., additional, Achermann, John C., additional, and Buonocore, Federica, additional
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- 2022
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30. STXBP1Stop‐Loss Mutation Associated with Complex Early Onset Movement Disorder without Epilepsy
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Spaull, Robert, primary, Steel, Dora, additional, Barwick, Katy, additional, Prabhakar, Prab, additional, Wakeling, Emma, additional, and Kurian, Manju A., additional
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- 2022
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31. Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension
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Hadinnapola, Charaka, Bleda, Marta, Haimel, Matthias, Screaton, Nicholas, Swift, Andrew, Dorfmüller, Peter, Preston, Stephen D., Southwood, Mark, Hernandez-Sanchez, Jules, Martin, Jennifer, Treacy, Carmen, Yates, Katherine, Bogaard, Harm, Church, Colin, Coghlan, Gerry, Condliffe, Robin, Corris, Paul A., Gibbs, Simon, Girerd, Barbara, Holden, Simon, Humbert, Marc, Kiely, David G., Lawrie, Allan, Machado, Rajiv, MacKenzie Ross, Robert, Moledina, Shahin, Montani, David, Newnham, Michael, Peacock, Andrew, Pepke-Zaba, Joanna, Rayner-Matthews, Paula, Shamardina, Olga, Soubrier, Florent, Southgate, Laura, Suntharalingam, Jay, Toshner, Mark, Trembath, Richard, Noordegraaf, Anton Vonk, Wilkins, Martin R., Wort, Stephen J., Wharton, John, Gräf, Stefan, Morrell, Nicholas W., Aitman, Timothy, Bennett, David, Caulfield, Mark, Chinnery, Patrick, Gale, Daniel, Koziell, Ania, Kuijpers, Taco W, Laffan, Michael A, Maher, Eamonn, Markus, Hugh S, Ouwehand, Willem H, Perry, David, Raymond, F Lucy, Roberts, Irene, Smith, Kenneth, Thrasher, Adrian, Watkins, Hugh, Williamson, Catherine, Woods, Geoffrey, Ashford, Sofie, Bradley, John R, Fletcher, Debra, Hammerton, Tracey, James, Roger, Kingston, Nathalie, Ouwehand, Willem H, Penkett, Christopher J, Raymond, F Lucy, Stirrups, Kathleen, Veltman, Marijke, Young, Tim, Ashford, Sofie, Brown, Matthew, Clements-Brod, Naomi, Davis, John, Dewhurst, Eleanor, Erwood, Marie, Frary, Amy, Linger, Rachel, Papadia, Sofia, Rehnstrom, Karola, Stark, Hannah, Allsup, David, Austin, Steve, Bakchoul, Tamam, Bariana, Tadbir K, Bolton-Maggs, Paula, Chalmers, Elizabeth, Collins, Peter, Erber, Wendy N, Everington, Tamara, Favier, Remi, Freson, Kathleen, Furie, Bruce, Gattens, Michael, Gomez, Keith, Greene, Daniel, Greinacher, Andreas, Hart, Daniel, Heemskerk, Johan WM, Henskens, Yvonne, Kazmi, Rashid, Keeling, David, Kelly, Anne M, Laffan, Michael A, Lambert, Michele P, Lentaigne, Claire, Liesner, Ri, Mangles, Sarah, Mathias, Mary, Millar, Carolyn M, Mumford, Andrew, Nurden, Paquita, Ouwehand, Willem H, Papadia, Sofia, Payne, Jeanette, Pasi, John, Perry, David J, Peerlinck, Kathelijne, Richards, Michael, Rondina, Matthew, Roughley, Catherine, Schulman, Sol, Schulze, Harald, Scully, Marie, Sivapalaratnam, Suthesh, Tait, R Campbell, Talks, Kate, Thachil, Jecko, Turro, Ernest, Toh, Cheng-Hock, Van Geet, Chris, De Vries, Minka, Warner, Timothy Q, Westbury, Sarah, Furnell, Abigail, Mapeta, Rutendo, Simeoni, Ilenia, Staines, Simon, Stephens, Jonathan, Stirrups, Kathleen, Whitehorn, Deborah, Watt, Christopher, Attwood, Antony, Daugherty, Louise, Deevi, Sri VV, Halmagyi, Csaba, Hu, Fengyuan, James, Roger, Matser, Vera, Meacham, Stuart, Megy, Karyn, Penkett, Christopher J, Stirrups, Kathleen, Titterton, Catherine, Tuna, Salih, Yu, Ping, von Ziegenweldt, Julie, Astle, William, Carss, Keren, Greene, Daniel, Lango-Allen, Hana, Turro, Ernest, Astle, William, Greene, Daniel, Richardson, Sylvia, Turro, Ernest, Calleja, Paul, Rankin, Stuart, Turek, Wojciech, Bryson, Christine, Anderson, Julie, Fletcher, Debra, McJannet, Coleen, Stock, Sophie, Young, Tim, Wassmer, Evangeline, Sohal, Aman, Santra, Saikat, Vogt, Julie, Chitre, Manali, Krishnakumar, Deepa, Ambegaonkar, Gautum, Maw, Anna, Armstrong, Ruth, Park, Soo-Mi, Mehta, Sarju, Paterson, Joan, Carmichael, Jenny, Allen, Louise, Hensiek, Anke, Firth, Helen, Stein, Penelope, Deegan, Patrick, Doffinger, Rainer, Parker, Alasdair, Bitner-Glindzicz, Maria, Scott, Richard, Hurst, Jane, Rosser, Elisabeth, Lees, Melissa, Clement, Emma, Henderson, Robert, Thompson, Dorothy, Gardham, Alice, Gissen, Paul, Josifova, Dragana, Thomas, Ellen, Patch, Chris, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Canham, Natalie, Wakeling, Emma, Holder, Susan, Ghali, Neeti, Brady, Angie, Clowes, Virginia, MacLaren, Robert, Webster, Andrew, Moore, Anthony, Arno, Gavin, Michaelides, Michel, Rankin, Julia, Kurian, Manju, Murphy, Elaine, Carss, Keren, Sanchis-Juan, Alba, Erwood, Marie, Dewhurst, Eleanor, Grozeva, Detelina, Raymond, F Lucy, Reid, Evan, Woods, Geoff, Tischkowitz, Marc, Sandford, Richard, Ali, Sonia, Creaser-Myers, Amanda, Cookson, Victoria, DaCosta, Rosa, Dormand, Natalie, Ghataorhe, Pavandeep K, Greenhalgh, Alan, Huis in’t Veld, Anna, Kennedy, Fiona, Mackenzie Ross, Rob, Masati, Larahmie, Meehan, Sharon, Othman, Shokri, Pollock, Val, Polwarth, Gary, Rhodes, Christopher J, Rue-Albrecht, Kevin, Schotte, Gwen, Shipley, Debbie, Tan, Yvonne, Wanjiku, Ivy, Wort, John, Smith, Kenneth, Kuijpers, Taco, Thrasher, Adrian, Thaventhiran, James, Brown, Matthew, Lango Allen, Hana, Simeoni, Ilenia, Staples, Emily, Samarghitean, Crina, Alachkar, Hana, Antrobus, Richard, Arumugakani, Gururaj, Bacchelli, Chiara, Baxendale, Helen, Bethune, Claire, Bibi, Shahnaz, Booth, Claire, Browning, Michael, Burns, Siobhan, Chandra, Anita, Cooper, Nichola, Davies, Sophie, Devlin, Lisa, Doffinger, Rainer, Drewe, Elizabeth, Edgar, David, Egner, William, Ghurye, Rohit, Gilmour, Kimberley, Goddard, Sarah, Gordins, Pavel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Hayman, Grant, Herwadkar, Archana, Huissoon, Aarnoud, Jolles, Stephen, Kelleher, Peter, Kumararatne, Dinakantha, Lear, Sara, Longhurst, Hilary, Lorenzo, Lorena, Maimaris, Jesmeen, Manson, Ania, McDermott, Elizabeth, Murng, Sai, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Richter, Alex, Sargur, Ravishankar, Savic, Sinisa, Seneviratne, Suranjith, Sewell, Carrock, Stauss, Hans, Thomas, Moira, Welch, Steve, Willcocks, Lisa, Yeatman, Nigel, and Yong, Patrick
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- 2017
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32. Prevalence and architecture of de novo mutations in developmental disorders
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McRae, Jeremy F., Clayton, Stephen, Fitzgerald, Tomas W., Kaplanis, Joanna, Prigmore, Elena, Rajan, Diana, Sifrim, Alejandro, Aitken, Stuart, Akawi, Nadia, Alvi, Mohsan, Ambridge, Kirsty, Barrett, Daniel M., Bayzetinova, Tanya, Jones, Philip, Jones, Wendy D., King, Daniel, Krishnappa, Netravathi, Mason, Laura E., Singh, Tarjinder, Tivey, Adrian R., Ahmed, Munaza, Anjum, Uruj, Archer, Hayley, Armstrong, Ruth, Awada, Jana, Balasubramanian, Meena, Banka, Siddharth, Baralle, Diana, Barnicoat, Angela, Batstone, Paul, Baty, David, Bennett, Chris, Berg, Jonathan, Bernhard, Birgitta, Bevan, Paul A., Bitner-Glindzicz, Maria, Blair, Edward, Blyth, Moira, Bohanna, David, Bourdon, Louise, Bourn, David, Bradley, Lisa, Brady, Angela, Brent, Simon, Brewer, Carole, Brunstrom, Kate, Bunyan, David J., Burn, John, Canham, Natalie, Castle, Bruce, Chandler, Kate, Chatzimichali, Elena, Cilliers, Deirdre, Clarke, Angus, Clasper, Susan, Clayton-Smith, Jill, Clowes, Virginia, Coates, Andrea, Cole, Trevor, Colgiu, Irina, Collins, Amanda, Collinson, Morag N., Connell, Fiona, Cooper, Nicola, Cox, Helen, Cresswell, Lara, Cross, Gareth, Crow, Yanick, D’Alessandro, Mariella, Dabir, Tabib, Davidson, Rosemarie, Davies, Sally, de Vries, Dylan, Dean, John, Deshpande, Charu, Devlin, Gemma, Dixit, Abhijit, Dobbie, Angus, Donaldson, Alan, Donnai, Dian, Donnelly, Deirdre, Donnelly, Carina, Douglas, Angela, Douzgou, Sofia, Duncan, Alexis, Eason, Jacqueline, Ellard, Sian, Ellis, Ian, Elmslie, Frances, Evans, Karenza, Everest, Sarah, Fendick, Tina, Fisher, Richard, Flinter, Frances, Foulds, Nicola, Fry, Andrew, Fryer, Alan, Gardiner, Carol, Gaunt, Lorraine, Ghali, Neeti, Gibbons, Richard, Gill, Harinder, Goodship, Judith, Goudie, David, Gray, Emma, Green, Andrew, Greene, Philip, Greenhalgh, Lynn, Gribble, Susan, Harrison, Rachel, Harrison, Lucy, Harrison, Victoria, Hawkins, Rose, He, Liu, Hellens, Stephen, Henderson, Alex, Hewitt, Sarah, Hildyard, Lucy, Hobson, Emma, Holden, Simon, Holder, Muriel, Holder, Susan, Hollingsworth, Georgina, Homfray, Tessa, Humphreys, Mervyn, Hurst, Jane, Hutton, Ben, Ingram, Stuart, Irving, Melita, Islam, Lily, Jackson, Andrew, Jarvis, Joanna, Jenkins, Lucy, Johnson, Diana, Jones, Elizabeth, Josifova, Dragana, Joss, Shelagh, Kaemba, Beckie, Kazembe, Sandra, Kelsell, Rosemary, Kerr, Bronwyn, Kingston, Helen, Kini, Usha, Kinning, Esther, Kirby, Gail, Kirk, Claire, Kivuva, Emma, Kraus, Alison, Kumar, Dhavendra, Ajith Kumar, V. K., Lachlan, Katherine, Lam, Wayne, Lampe, Anne, Langman, Caroline, Lees, Melissa, Lim, Derek, Longman, Cheryl, Lowther, Gordon, Lynch, Sally A., Magee, Alex, Maher, Eddy, Male, Alison, Mansour, Sahar, Marks, Karen, Martin, Katherine, Maye, Una, McCann, Emma, McConnell, Vivienne, McEntagart, Meriel, McGowan, Ruth, McKay, Kirsten, McKee, Shane, McMullan, Dominic J., McNerlan, Susan, McWilliam, Catherine, Mehta, Sarju, Metcalfe, Kay, Middleton, Anna, Miedzybrodzka, Zosia, Miles, Emma, Mohammed, Shehla, Montgomery, Tara, Moore, David, Morgan, Sian, Morton, Jenny, Mugalaasi, Hood, Murday, Victoria, Murphy, Helen, Naik, Swati, Nemeth, Andrea, Nevitt, Louise, Newbury-Ecob, Ruth, Norman, Andrew, O’Shea, Rosie, Ogilvie, Caroline, Ong, Kai-Ren, Park, Soo-Mi, Parker, Michael J., Patel, Chirag, Paterson, Joan, Payne, Stewart, Perrett, Daniel, Phipps, Julie, Pilz, Daniela T., Pollard, Martin, Pottinger, Caroline, Poulton, Joanna, Pratt, Norman, Prescott, Katrina, Price, Sue, Pridham, Abigail, Procter, Annie, Purnell, Hellen, Quarrell, Oliver, Ragge, Nicola, Rahbari, Raheleh, Randall, Josh, Rankin, Julia, Raymond, Lucy, Rice, Debbie, Robert, Leema, Roberts, Eileen, Roberts, Jonathan, Roberts, Paul, Roberts, Gillian, Ross, Alison, Rosser, Elisabeth, Saggar, Anand, Samant, Shalaka, Sampson, Julian, Sandford, Richard, Sarkar, Ajoy, Schweiger, Susann, Scott, Richard, Scurr, Ingrid, Selby, Ann, Seller, Anneke, Sequeira, Cheryl, Shannon, Nora, Sharif, Saba, Shaw-Smith, Charles, Shearing, Emma, Shears, Debbie, Sheridan, Eamonn, Simonic, Ingrid, Singzon, Roldan, Skitt, Zara, Smith, Audrey, Smith, Kath, Smithson, Sarah, Sneddon, Linda, Splitt, Miranda, Squires, Miranda, Stewart, Fiona, Stewart, Helen, Straub, Volker, Suri, Mohnish, Sutton, Vivienne, Swaminathan, Ganesh Jawahar, Sweeney, Elizabeth, Tatton-Brown, Kate, Taylor, Cat, Taylor, Rohan, Tein, Mark, Temple, Karen I., Thomson, Jenny, Tischkowitz, Marc, Tomkins, Susan, Torokwa, Audrey, Treacy, Becky, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Vandersteen, Anthony, Varghese, Vinod, Vasudevan, Pradeep, Vijayarangakannan, Parthiban, Vogt, Julie, Wakeling, Emma, Wallwark, Sarah, Waters, Jonathon, Weber, Astrid, Wellesley, Diana, Whiteford, Margo, Widaa, Sara, Wilcox, Sarah, Wilkinson, Emily, Williams, Denise, Williams, Nicola, Wilson, Louise, Woods, Geoff, Wragg, Christopher, Wright, Michael, Yates, Laura, Yau, Michael, Nellåker, Chris, Parker, Michael, Firth, Helen V., Wright, Caroline F., FitzPatrick, David R., Barrett, Jeffrey C., and Hurles, Matthew E.
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- 2017
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33. EXPERT CONSENSUS DOCUMENT: Diagnosis and management of Silver-Russell syndrome: first international consensus statement
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Wakeling, Emma L., Brioude, Frédéric, Lokulo-Sodipe, Oluwakemi, OʼConnell, Susan M., Salem, Jennifer, Bliek, Jet, Canton, Ana P. M., Chrzanowska, Krystyna H., Davies, Justin H., Dias, Renuka P., Dubern, Béatrice, Elbracht, Miriam, Giabicani, Eloise, Grimberg, Adda, Grønskov, Karen, Hokken-Koelega, Anita C. S., Jorge, Alexander A., Kagami, Masayo, Linglart, Agnes, Maghnie, Mohamad, Mohnike, Klaus, Monk, David, Moore, Gudrun E., Murray, Philip G., Ogata, Tsutomu, Petit, Isabelle Oliver, Russo, Silvia, Said, Edith, Toumba, Meropi, Tümer, Zeynep, Binder, Gerhard, Eggermann, Thomas, Harbison, Madeleine D., Temple, Karen I., Mackay, Deborah J. G., and Netchine, Irène
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- 2017
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34. Recognizing vascular Ehlers–Danlos syndrome (type IV) in the newborn
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McKenna, Caoimhe, Vandersteen, Anthony, Wakeling, Emma, Pope, Francis M., and Ghali, Neeti
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- 2017
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35. Publisher Correction: BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome
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Olley, Gabrielle, Ansari, Morad, Bengani, Hemant, Grimes, Graeme R., Rhodes, James, von Kriegsheim, Alex, Blatnik, Ana, Stewart, Fiona J., Wakeling, Emma, Carroll, Nicola, Ross, Alison, Park, Soo-Mi, Deciphering Developmental Disorders Study, Bickmore, Wendy A., Pradeepa, Madapura M., and FitzPatrick, David R.
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- 2019
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36. 127 ACTA1 associated myopathy with neurogenic EMG changes
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Doherty, Carolynne, primary, Blake, Julian, additional, Manzur, Adnan, additional, Wakeling, Emma, additional, Shah, Sachit, additional, Muntoni, Francesco, additional, and Reilly, Mary, additional
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- 2022
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37. Multicenter Consensus Approach to Evaluation of Neonatal Hypotonia in the Genomic Era: A Review
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Morton, Sarah U., primary, Christodoulou, John, additional, Costain, Gregory, additional, Muntoni, Francesco, additional, Wakeling, Emma, additional, Wojcik, Monica H., additional, French, Courtney E., additional, Szuto, Anna, additional, Dowling, James J., additional, Cohn, Ronald D., additional, Raymond, F. Lucy, additional, Darras, Basil T., additional, Williams, David A., additional, Lunke, Sebastian, additional, Stark, Zornitza, additional, Rowitch, David H., additional, and Agrawal, Pankaj B., additional
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- 2022
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38. Height and body mass index in molecularly confirmed Silver–Russell syndrome and the long‐term effects of growth hormone treatment
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Lokulo‐Sodipe, Oluwakemi, primary, Giabicani, Eloïse, additional, Canton, Ana P. M., additional, Ferrand, Nawfel, additional, Child, Jenny, additional, Wakeling, Emma L., additional, Binder, Gerhard, additional, Netchine, Irène, additional, Mackay, Deborah J. G., additional, Inskip, Hazel M., additional, Byrne, Christopher D., additional, Temple, I. Karen, additional, and Davies, Justin H., additional
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- 2022
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39. Identification of a homozygous nonsense mutation in KIAA0556 in a consanguineous family displaying Joubert syndrome
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Roosing, Susanne, Rosti, Rasim O., Rosti, Basak, de Vrieze, Erik, Silhavy, Jennifer L., van Wijk, Erwin, Wakeling, Emma, and Gleeson, Joseph G.
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- 2016
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40. 30 Rapid trio whole exome sequencing (R14) of an undiagnosed child, in the context of a new pregnancy
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Koutsogianni, Maria, primary, Wakeling, Emma, additional, Male, Alison, additional, Stals, Karen, additional, and Ashraf, Tazeen, additional
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- 2021
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41. Baseline and post prophylactic tubal–ovarian surgery CA125 levels in BRCA1 and BRCA2 mutation carriers
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Chen, Ying, Bancroft, Elizabeth, Ashley, Sue, Arden-Jones, Audrey, Thomas, Sarah, Shanley, Susan, Saya, Sibel, Wakeling, Emma, Eeles, Rosalind, and The Carrier Clinic Collaborators
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- 2014
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42. Cerebro–costo–mandibular syndrome: Clinical, radiological, and genetic findings
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Tooley, Madeleine, Lynch, Danielle, Bernier, Francois, Parboosingh, Jillian, Bhoj, Elizabeth, Zackai, Elaine, Calder, Alistair, Itasaki, Nobue, Wakeling, Emma, Scott, Richard, Lees, Melissa, Clayton-Smith, Jill, Blyth, Moira, Morton, Jenny, Shears, Debbie, Kini, Usha, Homfray, Tessa, Clarke, Angus, Barnicoat, Angela, Wallis, Colin, Hewitson, Rebecca, Offiah, Amaka, Saunders, Michael, Langton-Hewer, Simon, Hilliard, Tom, Davis, Peter, and Smithson, Sarah
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- 2016
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43. CCDC88A mutations cause PEHO-like syndrome in humans and mouse
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Nahorski, Michael S., Asai, Masato, Wakeling, Emma, Parker, Alasdair, Asai, Naoya, Canham, Natalie, Holder, Susan E., Chen, Ya-Chun, Dyer, Joshua, Brady, Angela F., Takahashi, Masahide, and Woods, C. Geoffrey
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- 2016
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44. Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model
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Jurkute, Neringa, Bertacchi, Michele, Arno, Gavin, Tocco, Chiara, Kim, Ungsoo Samuel, Kruszewski, Adam M, Avery, Robert A, Bedoukian, Emma C, Han, Jinu, Ahn, Sung Jun, Pontikos, Nikolas, Acheson, James, Davagnanam, Indran, Bowman, Richard, Kaliakatsos, Marios, Gardham, Alice, Wakeling, Emma, Oluonye, Ngozi, Reddy, Maddy Ashwin, Clark, Elaine, Rosser, Elisabeth, Amati-Bonneau, Patrizia, Charif, Majida, Lenaers, Guy, Meunier, Isabelle, Defoort, Sabine, Vincent-Delorme, Catherine, Robson, Anthony G, Holder, Graham E, Jeanjean, Luc, Martinez-Monseny, Antonio, Vidal-Santacana, Mariona, Dominici, Chloé, Gaggioli, Cedric, Giordano, Nadia, Caleo, Matteo, Liu, Grant T, Genomics England Research Consortium, Webster, Andrew R, Studer, Michèle, Yu-Wai-Man, Patrick, Jurkute, Neringa [0000-0002-3092-7451], Tocco, Chiara [0000-0002-2616-0198], Han, Jinu [0000-0002-8607-6625], Pontikos, Nikolas [0000-0003-1782-4711], Studer, Michèle [0000-0001-7105-2957], and Apollo - University of Cambridge Repository
- Subjects
genetic structures ,inherited optic neuropathy ,mouse model ,BBSOAS ,sense organs ,eye diseases ,optic nerve head anomalies ,NR2F1 - Abstract
Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system.
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- 2021
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45. Dominant and recessiveSLC12A2‐syndrome
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McNeill, Alisdair, primary, Aurora, Paul, additional, Rajput, Kaukab, additional, Nash, Robert, additional, Stals, Karen, additional, Robinson, Hannah, additional, and Wakeling, Emma, additional
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- 2021
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46. Body composition in adults with genetically-confirmed Silver-Russell syndrome.
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Lokulo-Sodipe, Oluwakemi, primary, Inskip, Hazel. M., additional, Byrne, Christopher D., additional, Child, Jenny, additional, Wakeling, Emma L., additional, Mackay, Deborah J.G., additional, Temple, I. Karen, additional, and Davies, Justin H., additional
- Published
- 2021
- Full Text
- View/download PDF
47. Publisher Correction: BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome
- Author
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Olley, Gabrielle, Ansari, Morad, Bengani, Hemant, Grimes, Graeme R., Rhodes, James, von Kriegsheim, Alex, Blatnik, Ana, Stewart, Fiona J., Wakeling, Emma, Carroll, Nicola, Ross, Alison, Park, Soo-Mi, Bickmore, Wendy A., Pradeepa, Madapura M., FitzPatrick, David R., and Deciphering Developmental Disorders Study
- Published
- 2018
- Full Text
- View/download PDF
48. Author Correction: CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language
- Author
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Snijders Blok, Lot, Rousseau, Justine, Twist, Joanna, Ehresmann, Sophie, Takaku, Motoki, Venselaar, Hanka, Rodan, Lance H., Nowak, Catherine B., Douglas, Jessica, Swoboda, Kathryn J., Steeves, Marcie A., Sahai, Inderneel, Stumpel, Connie T. R. M., Stegmann, Alexander P. A., Wheeler, Patricia, Willing, Marcia, Fiala, Elise, Kochhar, Aaina, Gibson, William T., Cohen, Ana S. A., Agbahovbe, Ruky, Innes, A. Micheil, Au, P. Y. Billie, Rankin, Julia, Anderson, Ilse J., Skinner, Steven A., Louie, Raymond J., Warren, Hannah E., Afenjar, Alexandra, Keren, Boris, Nava, Caroline, Buratti, Julien, Isapof, Arnaud, Rodriguez, Diana, Lewandowski, Raymond, Propst, Jennifer, van Essen, Ton, Choi, Murim, Lee, Sangmoon, Chae, Jong H., Price, Susan, Schnur, Rhonda E., Douglas, Ganka, Wentzensen, Ingrid M., Zweier, Christiane, Reis, André, Bialer, Martin G., Moore, Christine, Koopmans, Marije, Brilstra, Eva H., Monroe, Glen R., van Gassen, Koen L. I., van Binsbergen, Ellen, Newbury-Ecob, Ruth, Bownass, Lucy, Bader, Ingrid, Mayr, Johannes A., Wortmann, Saskia B., Jakielski, Kathy J., Strand, Edythe A., Kloth, Katja, Bierhals, Tatjana, McRae, Jeremy F., Clayton, Stephen, Fitzgerald, Tomas W., Kaplanis, Joanna, Prigmore, Elena, Rajan, Diana, Sifrim, Alejandro, Aitken, Stuart, Akawi, Nadia, Alvi, Mohsan, Ambridge, Kirsty, Barrett, Daniel M., Bayzetinova, Tanya, Jones, Philip, Jones, Wendy D., King, Daniel, Krishnappa, Netravathi, Mason, Laura E., Singh, Tarjinder, Tivey, Adrian R., Ahmed, Munaza, Anjum, Uruj, Archer, Hayley, Armstrong, Ruth, Awada, Jana, Balasubramanian, Meena, Banka, Siddharth, Baralle, Diana, Barnicoat, Angela, Batstone, Paul, Baty, David, Bennett, Chris, Berg, Jonathan, Bernhard, Birgitta, Bevan, A. Paul, Bitner-Glindzicz, Maria, Blair, Edward, Blyth, Moira, Bohanna, David, Bourdon, Louise, Bourn, David, Bradley, Lisa, Brady, Angela, Brent, Simon, Brewer, Carole, Brunstrom, Kate, Bunyan, David J., Burn, John, Canham, Natalie, Castle, Bruce, Chandler, Kate, Chatzimichali, Elena, Cilliers, Deirdre, Clarke, Angus, Clasper, Susan, Clayton-Smith, Jill, Clowes, Virginia, Coates, Andrea, Cole, Trevor, Colgiu, Irina, Collins, Amanda, Collinson, Morag N., Connell, Fiona, Cooper, Nicola, Cox, Helen, Cresswell, Lara, Cross, Gareth, Crow, Yanick, D’Alessandro, Mariella, Dabir, Tabib, Davidson, Rosemarie, Davies, Sally, de Vries, Dylan, Dean, John, Deshpande, Charu, Devlin, Gemma, Dixit, Abhijit, Dobbie, Angus, Donaldson, Alan, Donnai, Dian, Donnelly, Deirdre, Donnelly, Carina, Douglas, Angela, Douzgou, Sofia, Duncan, Alexis, Eason, Jacqueline, Ellard, Sian, Ellis, Ian, Elmslie, Frances, Evans, Karenza, Everest, Sarah, Fendick, Tina, Fisher, Richard, Flinter, Frances, Foulds, Nicola, Fry, Andrew, Fryer, Alan, Gardiner, Carol, Gaunt, Lorraine, Ghali, Neeti, Gibbons, Richard, Gill, Harinder, Goodship, Judith, Goudie, David, Gray, Emma, Green, Andrew, Greene, Philip, Greenhalgh, Lynn, Gribble, Susan, Harrison, Rachel, Harrison, Lucy, Harrison, Victoria, Hawkins, Rose, He, Liu, Hellens, Stephen, Henderson, Alex, Hewitt, Sarah, Hildyard, Lucy, Hobson, Emma, Holden, Simon, Holder, Muriel, Holder, Susan, Hollingsworth, Georgina, Homfray, Tessa, Humphreys, Mervyn, Hurst, Jane, Hutton, Ben, Ingram, Stuart, Irving, Melita, Islam, Lily, Jackson, Andrew, Jarvis, Joanna, Jenkins, Lucy, Johnson, Diana, Jones, Elizabeth, Josifova, Dragana, Joss, Shelagh, Kaemba, Beckie, Kazembe, Sandra, Kelsell, Rosemary, Kerr, Bronwyn, Kingston, Helen, Kini, Usha, Kinning, Esther, Kirby, Gail, Kirk, Claire, Kivuva, Emma, Kraus, Alison, Kumar, Dhavendra, Kumar, V. K. Ajith, Lachlan, Katherine, Lam, Wayne, Lampe, Anne, Langman, Caroline, Lees, Melissa, Lim, Derek, Longman, Cheryl, Lowther, Gordon, Lynch, Sally A., Magee, Alex, Maher, Eddy, Male, Alison, Mansour, Sahar, Marks, Karen, Martin, Katherine, Maye, Una, McCann, Emma, McConnell, Vivienne, McEntagart, Meriel, McGowan, Ruth, McKay, Kirsten, McKee, Shane, McMullan, Dominic J., McNerlan, Susan, McWilliam, Catherine, Mehta, Sarju, Metcalfe, Kay, Middleton, Anna, Miedzybrodzka, Zosia, Miles, Emma, Mohammed, Shehla, Montgomery, Tara, Moore, David, Morgan, Sian, Morton, Jenny, Mugalaasi, Hood, Murday, Victoria, Murphy, Helen, Naik, Swati, Nemeth, Andrea, Nevitt, Louise, Norman, Andrew, O’Shea, Rosie, Ogilvie, Caroline, Ong, Kai-Ren, Park, Soo-Mi, Parker, Michael J., Patel, Chirag, Paterson, Joan, Payne, Stewart, Perrett, Daniel, Phipps, Julie, Pilz, Daniela T., Pollard, Martin, Pottinger, Caroline, Poulton, Joanna, Pratt, Norman, Prescott, Katrina, Pridham, Abigail, Procter, Annie, Purnell, Hellen, Quarrell, Oliver, Ragge, Nicola, Rahbari, Raheleh, Randall, Josh, Raymond, Lucy, Rice, Debbie, Robert, Leema, Roberts, Eileen, Roberts, Jonathan, Roberts, Paul, Roberts, Gillian, Ross, Alison, Rosser, Elisabeth, Saggar, Anand, Samant, Shalaka, Sampson, Julian, Sandford, Richard, Sarkar, Ajoy, Schweiger, Susann, Scott, Richard, Scurr, Ingrid, Selby, Ann, Seller, Anneke, Sequeira, Cheryl, Shannon, Nora, Sharif, Saba, Shaw-Smith, Charles, Shearing, Emma, Shears, Debbie, Sheridan, Eamonn, Simonic, Ingrid, Singzon, Roldan, Skitt, Zara, Smith, Audrey, Smith, Kath, Smithson, Sarah, Sneddon, Linda, Splitt, Miranda, Squires, Miranda, Stewart, Fiona, Stewart, Helen, Straub, Volker, Suri, Mohnish, Sutton, Vivienne, Swaminathan, Ganesh Jawahar, Sweeney, Elizabeth, Tatton-Brown, Kate, Taylor, Cat, Taylor, Rohan, Tein, Mark, Temple, I. Karen, Thomson, Jenny, Tischkowitz, Marc, Tomkins, Susan, Torokwa, Audrey, Treacy, Becky, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Vandersteen, Anthony, Varghese, Vinod, Vasudevan, Pradeep, Vijayarangakannan, Parthiban, Vogt, Julie, Wakeling, Emma, Wallwark, Sarah, Waters, Jonathon, Weber, Astrid, Wellesley, Diana, Whiteford, Margo, Widaa, Sara, Wilcox, Sarah, Wilkinson, Emily, Williams, Denise, Williams, Nicola, Wilson, Louise, Woods, Geoff, Wragg, Christopher, Wright, Michael, Yates, Laura, Yau, Michael, Nellåker, Chris, Parker, Michael, Firth, Helen V., Wright, Caroline F., FitzPatrick, David R., Barrett, Jeffrey C., Hurles, Matthew E., Roberts, John D., Petrovich, Robert M., Machida, Shinichi, Kurumizaka, Hitoshi, Lelieveld, Stefan, Pfundt, Rolph, Jansen, Sandra, Deriziotis, Pelagia, Faivre, Laurence, Thevenon, Julien, Assoum, Mirna, Shriberg, Lawrence, Kleefstra, Tjitske, Brunner, Han G., Wade, Paul A., Fisher, Simon E., and Campeau, Philippe M.
- Subjects
Male ,Models, Molecular ,Developmental Disabilities ,Gene Expression ,General Physics and Astronomy ,02 engineering and technology ,Chromatin remodelling ,Sociology ,lcsh:Science ,Independent research ,Adenosine Triphosphatases ,0303 health sciences ,Multidisciplinary ,biology ,Health innovation ,Disease genetics ,Published Erratum ,Neurodevelopmental disorders ,021001 nanoscience & nanotechnology ,Spelling ,3. Good health ,Phenotype ,General partnership ,Child, Preschool ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Female ,medicine.symptom ,Construct (philosophy) ,0210 nano-technology ,Psychology ,Mi-2 Nucleosome Remodeling and Deacetylase Complex ,Clinical epigenetics ,Genotype ,Science ,Mutation, Missense ,Library science ,Child health ,Speech Disorders ,General Biochemistry, Genetics and Molecular Biology ,Domain (software engineering) ,03 medical and health sciences ,Protein Domains ,Intellectual Disability ,medicine ,Humans ,Author Correction ,030304 developmental biology ,Research ethics ,Language Disorders ,Whole Genome Sequencing ,Core Grant ,Macrocephaly ,DNA Helicases ,Helicase ,General Chemistry ,Chromatin Assembly and Disassembly ,Megalencephaly ,HEK293 Cells ,biology.protein ,lcsh:Q ,Neuroscience ,Impaired speech - Abstract
An Author Correction to this article was published on 15 February 2019 An Author Correction to this article was published on 02 May 2019 We thank all individuals and families for their contribution. We thank Amaia Carrion Castillo and Else Eising for assistance with the WGS analysis of the index individual, and Sarah Graham and Elliot Sollis for cloning the wild-type CHD3 construct for immunofluorescence. This work was supported by the Netherlands Organization for Scientific Research (NWO) Gravitation Grant 24.001.006 to the Language in Interaction Consortium (L.S.B., S.E.F., and H.G.B.), the Max Planck Society (S.E.F.), the National Institute on Deafness and Other Communication Disorders Grant DC000496 (L.Sh.) and a core grant to the Waisman Center from the National Institute of Child Health and Human Development (Grant U54 HD090256) to L.Sh., the Canadian Institutes of Health Research Grants MOP-119595 and PJT-148830 to W.T.G. Individuals 11, 16, 24, and 28 were part of The DDD Study cohort. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund [Grant number HICF-1009-003], a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute [Grant number WT098051]. The views expressed in this publication are those of the author(s) and not necessarily those of the Wellcome Trust or the Department of Health. The DDD study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.
- Published
- 2019
49. DOCK6 Mutations Are Responsible for a Distinct Autosomal-Recessive Variant of Adams–Oliver Syndrome Associated with Brain and Eye Anomalies
- Author
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Sukalo, Maja, Tilsen, Felix, Kayserili, Hülya, Müller, Dietmar, Tüysüz, Beyhan, Ruddy, Deborah M., Wakeling, Emma, rstavik, Karen Helene, Snape, Katie M., Trembath, Richard, De Smedt, Maryse, van der Aa, Nathalie, Skalej, Martin, Mundlos, Stefan, Wuyts, Wim, Southgate, Laura, and Zenker, Martin
- Published
- 2015
- Full Text
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50. Mosaic structural variation in children with developmental disorders
- Author
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King, Daniel A., Jones, Wendy D., Crow, Yanick J., Dominiczak, Anna F., Foster, Nicola A., Gaunt, Tom R., Harris, Jade, Hellens, Stephen W., Homfray, Tessa, Innes, Josie, Jones, Elizabeth A., Joss, Shelagh, Kulkarni, Abhijit, Mansour, Sahar, Morris, Andrew D., Parker, Michael J., Porteous, David J., Shihab, Hashem A., Smith, Blair H., Tatton-Brown, Katrina, Tolmie, John L., Trzaskowski, Maciej, Vasudevan, Pradeep C., Wakeling, Emma, Wright, Michael, Plomin, Robert, Timpson, Nicholas J., and Hurles, Matthew E.
- Published
- 2015
- Full Text
- View/download PDF
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