Search

Your search keyword '"Kerr, Bronwyn"' showing total 334 results
Start Over Author "Kerr, Bronwyn"
334 results on '"Kerr, Bronwyn"'

1. 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
Full Text
View/download PDF

2. DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes

Author

Choufani, Sanaa, Gibson, William T, Turinsky, Andrei L, Chung, Brian HY, Wang, Tianren, Garg, Kopal, Vitriolo, Alessandro, Cohen, Ana SA, Cyrus, Sharri, Goodman, Sarah, Chater-Diehl, Eric, Brzezinski, Jack, Brudno, Michael, Ming, Luk Ho, White, Susan M, Lynch, Sally Ann, Clericuzio, Carol, Temple, I Karen, Flinter, Frances, McConnell, Vivienne, Cushing, Tom, Bird, Lynne M, Splitt, Miranda, Kerr, Bronwyn, Scherer, Stephen W, Machado, Jerry, Imagawa, Eri, Okamoto, Nobuhiko, Matsumoto, Naomichi, Testa, Guiseppe, Iascone, Maria, Tenconi, Romano, Caluseriu, Oana, Mendoza-Londono, Roberto, Chitayat, David, Cytrynbaum, Cheryl, Tatton-Brown, Katrina, and Weksberg, Rosanna

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Rare Diseases, Abnormalities, Multiple, Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Congenital Hypothyroidism, Craniofacial Abnormalities, DNA Methylation, Enhancer of Zeste Homolog 2 Protein, Female, Hand Deformities, Congenital, Humans, Infant, Intellectual Disability, Male, Mosaicism, Mutation, Mutation, Missense, Neoplasm Proteins, Polycomb Repressive Complex 2, Reproducibility of Results, Transcription Factors, Young Adult, DNA methylation signature, EED, SUZ12, intellectual disability, overgrowth syndromes, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other core components of PRC2, and predict the presence of pathogenic variants in undiagnosed individuals with OGID. The discovery of a functionally relevant signature with utility for diagnostic classification of sequence variants in EZH2, EED, and SUZ12 supports the emerging paradigm shift for implementation of DNAm signatures into diagnostics and translational research.

Published
2020

3. Preventing Violence in the Raced Margins: Alternate Rationalities, Possibilities, and Imaginaries

Author

Dutta, Mohan J., primary, Elers, Phoebe, additional, Jayan, Pooja, additional, Rahman, Mahbubur, additional, Hashim, Shakila, additional, Liu, Jie, additional, Nematollahi, Negin, additional, Mohd Sharif, Akbar Shah Bin, additional, Teikmata-Tito, Christina, additional, Whittfield, Francine, additional, Bray, Stephen, additional, Holdaway, Sarah, additional, Jackson, De’Anne, additional, Kerr, Bronwyn, additional, Metuamate, Selina, additional, Pokaia, Venessa, additional, Raharuhi, Ihaia, additional, and Zorn, Andee, additional

Published
2024
Full Text
View/download PDF

4. Costello syndrome: Clinical phenotype, genotype, and management guidelines.

Author

Gripp, Karen W, Morse, Lindsey A, Axelrad, Marni, Chatfield, Kathryn C, Chidekel, Aaron, Dobyns, William, Doyle, Daniel, Kerr, Bronwyn, Lin, Angela E, Schwartz, David D, Sibbles, Barbara J, Siegel, Dawn, Shankar, Suma P, Stevenson, David A, Thacker, Mihir M, Weaver, K Nicole, White, Sue M, and Rauen, Katherine A

Subjects
Face, Heart, Humans, Heart Defects, Congenital, Abnormalities, Multiple, Developmental Disabilities, Gene Expression Regulation, Genotype, Phenotype, Germ-Line Mutation, Disease Management, Proto-Oncogene Proteins p21(ras), Guidelines as Topic, Costello Syndrome, Costello syndrome, HRAS mutation, RAS/MAPK, RASopathy, management guidelines, Genetics, Pediatric, Congenital Structural Anomalies, Health Services, Clinical Research, Management of diseases and conditions, 7.3 Management and decision making, Good Health and Well Being, RAS, MAPK, Clinical Sciences
Abstract

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence-based guidelines due to the lack of data for this rare condition.

Published
2019

5. First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics

Author

Rauen, Katherine A, Alsaegh, Abeer, Ben‐Shachar, Shay, Berman, Yemima, Blakeley, Jaishri, Cordeiro, Isabel, Elgersma, Ype, Evans, D Gareth, Fisher, Michael J, Frayling, Ian M, George, Joshi, Huson, Susan M, Kerr, Bronwyn, Khire, Uday, Korf, Bruce, Legius, Eric, Messiaen, Ludwine, van Minkelen, Rick, Nampoothiri, Sheela, Ngeow, Joanne, Parada, Luis F, Phadke, Shubha, Pillai, Ashok, Plotkin, Scott R, Puri, Ratna, Raji, Anup, Ramesh, Vijaya, Ratner, Nancy, Shankar, Suma P, Sharda, Sheetal, Tambe, Anant, Vikkula, Miikka, Widemann, Brigitte C, Wolkenstein, Pierre, and Upadhyaya, Meena

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Neurofibromatosis, Neurosciences, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Rare Diseases, Pediatric, Congenital, Biomarkers, Disease Management, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Mitogen-Activated Protein Kinases, Molecular Diagnostic Techniques, Molecular Targeted Therapy, Neurofibromatoses, Signal Transduction, Translational Research, Biomedical, ras Proteins, clinical trial, neurofibromatoses, RASopathy, signal transduction pathway, therapy, Clinical Sciences, Clinical sciences
Abstract

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio-facio-cutaneous syndrome, Legius syndrome, capillary malformation arterio-venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies.

Published
2019

6. Proceedings of the fifth international RASopathies symposium: When development and cancer intersect

Author

Rauen, Katherine A, Schoyer, Lisa, Schill, Lisa, Stronach, Beth, Albeck, John, Andresen, Brage S, Cavé, Hélène, Ellis, Michelle, Fruchtman, Steven M, Gelb, Bruce D, Gibson, Christopher C, Gripp, Karen, Hefner, Erin, Huang, William YC, Itkin, Maxim, Kerr, Bronwyn, Linardic, Corinne M, McMahon, Martin, Oberlander, Beverly, Perlstein, Ethan, Ratner, Nancy, Rogers, Leslie, Schenck, Annette, Shankar, Suma, Shvartsman, Stanislav, Stevenson, David A, Stites, Edward C, Stork, Philip JS, Sun, Cheng, Therrien, Marc, Ullian, Erik M, Widemann, Brigitte C, Yeh, Erika, Zampino, Giuseppe, Zenker, Martin, Timmer, William, and McCormick, Frank

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Animals, Gene Expression Regulation, Genetic Association Studies, Genetic Predisposition to Disease, Human Development, Humans, Models, Biological, Molecular Targeted Therapy, Neoplasms, Organogenesis, Signal Transduction, Syndrome, ras Proteins, cardio-facio-cutaneous syndrome, clinical trial, Costello syndrome, Legius syndrome, neurofibromatosis type 1, Noonan syndrome, RAS/MAPK, RASopathies, signal transduction pathway, therapy, Genetics, Clinical Sciences, Clinical sciences
Abstract

This report summarizes and highlights the fifth International RASopathies Symposium: When Development and Cancer Intersect, held in Orlando, Florida in July 2017. The RASopathies comprise a recognizable pattern of malformation syndromes that are caused by germ line mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. Because of their common underlying pathogenetic etiology, there is significant overlap in their phenotypic features, which includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, gastrointestinal and ocular abnormalities, neurological and neurocognitive issues, and a predisposition to cancer. The RAS pathway is a well-known oncogenic pathway that is commonly found to be activated in somatic malignancies. As in somatic cancers, the RASopathies can be caused by various pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. As such, the RASopathies represent an excellent model of study to explore the intersection of the effects of dysregulation and its consequence in both development and oncogenesis.

Published
2018

7. NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly

Author

Schanze, Ina, Bunt, Jens, Lim, Jonathan WC, Schanze, Denny, Dean, Ryan J, Alders, Marielle, Blanchet, Patricia, Attié-Bitach, Tania, Berland, Siren, Boogert, Steven, Boppudi, Sangamitra, Bridges, Caitlin J, Cho, Megan T, Dobyns, William B, Donnai, Dian, Douglas, Jessica, Earl, Dawn L, Edwards, Timothy J, Faivre, Laurence, Fregeau, Brieana, Genevieve, David, Gérard, Marion, Gatinois, Vincent, Holder-Espinasse, Muriel, Huth, Samuel F, Izumi, Kosuke, Kerr, Bronwyn, Lacaze, Elodie, Lakeman, Phillis, Mahida, Sonal, Mirzaa, Ghayda M, Morgan, Sian M, Nowak, Catherine, Peeters, Hilde, Petit, Florence, Pilz, Daniela T, Puechberty, Jacques, Reinstein, Eyal, Rivière, Jean-Baptiste, Santani, Avni B, Schneider, Anouck, Sherr, Elliott H, Smith-Hicks, Constance, Wieland, Ilse, Zackai, Elaine, Zhao, Xiaonan, Gronostajski, Richard M, Zenker, Martin, and Richards, Linda J

Subjects
Biomedical and Clinical Sciences, Mental Health, Pediatric, Intellectual and Developmental Disabilities (IDD), Neurosciences, Rare Diseases, Behavioral and Social Science, Genetics, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, Adolescent, Adult, Animals, Cerebral Cortex, Child, Child, Preschool, Codon, Nonsense, Cohort Studies, Corpus Callosum, Female, Haploinsufficiency, Humans, Intellectual Disability, Male, Megalencephaly, Mice, Mice, Knockout, NFI Transcription Factors, Polymorphism, Single Nucleotide, Young Adult, NFIB, agenesis of the corpus callosum, chromosome 9p22.3, chromosome 9p23, developmental delay, haploinsufficiency, intellectual disability, macrocephaly, megalencephaly, nuclear factor I, Biological Sciences, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly.

Published
2018

8. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder

Author

Reijnders, Margot RF, Miller, Kerry A, Alvi, Mohsan, Goos, Jacqueline AC, Lees, Melissa M, de Burca, Anna, Henderson, Alex, Kraus, Alison, Mikat, Barbara, de Vries, Bert BA, Isidor, Bertrand, Kerr, Bronwyn, Marcelis, Carlo, Schluth-Bolard, Caroline, Deshpande, Charu, Ruivenkamp, Claudia AL, Wieczorek, Dagmar, Study, The Deciphering Developmental Disorders, Baralle, Diana, Blair, Edward M, Engels, Hartmut, Lüdecke, Hermann-Josef, Eason, Jacqueline, Santen, Gijs WE, Clayton-Smith, Jill, Chandler, Kate, Tatton-Brown, Katrina, Payne, Katelyn, Helbig, Katherine, Radtke, Kelly, Nugent, Kimberly M, Cremer, Kirsten, Strom, Tim M, Bird, Lynne M, Sinnema, Margje, Bitner-Glindzicz, Maria, van Dooren, Marieke F, Alders, Marielle, Koopmans, Marije, Brick, Lauren, Kozenko, Mariya, Harline, Megan L, Klaassens, Merel, Steinraths, Michelle, Cooper, Nicola S, Edery, Patrick, Yap, Patrick, Terhal, Paulien A, van der Spek, Peter J, Lakeman, Phillis, Taylor, Rachel L, Littlejohn, Rebecca O, Pfundt, Rolph, Mercimek-Andrews, Saadet, Stegmann, Alexander PA, Kant, Sarina G, McLean, Scott, Joss, Shelagh, Swagemakers, Sigrid MA, Douzgou, Sofia, Wall, Steven A, Küry, Sébastien, Calpena, Eduardo, Koelling, Nils, McGowan, Simon J, Twigg, Stephen RF, Mathijssen, Irene MJ, Nellaker, Christoffer, Brunner, Han G, and Wilkie, Andrew OM

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Biotechnology, Brain Disorders, Human Genome, Neurosciences, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Base Sequence, Cell Line, Child, Child, Preschool, Facies, Female, Genetic Association Studies, Humans, Infant, Inheritance Patterns, Loss of Function Mutation, Male, Neurodevelopmental Disorders, Protein Kinases, RNA, Messenger, Translocation, Genetic, Young Adult, Deciphering Developmental Disorders Study, Tousled-like, facial averaging, haploinsufficiency, intellectual disability, kinase, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2.

Published
2018

10. The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway

Author

Stevenson, David A, Schill, Lisa, Schoyer, Lisa, Andresen, Brage S, Bakker, Annette, Bayrak-Toydemir, Pinar, Burkitt-Wright, Emma, Chatfield, Kathryn, Elefteriou, Florent, Elgersma, Ype, Fisher, Michael J, Franz, David, Gelb, Bruce D, Goriely, Anne, Gripp, Karen W, Hardan, Antonio Y, Keppler-Noreuil, Kim M, Kerr, Bronwyn, Korf, Bruce, Leoni, Chiara, McCormick, Frank, Plotkin, Scott R, Rauen, Katherine A, Reilly, Karlyne, Roberts, Amy, Sandler, Abby, Siegel, Dawn, Walsh, Karin, and Widemann, Brigitte C

Subjects
Biological Sciences, Genetics, Congenital Structural Anomalies, Neurosciences, Rare Diseases, Pediatric, Congenital, Capital Financing, Clinical Trials as Topic, Family, Genetic Diseases, Inborn, Humans, Intersectoral Collaboration, Mitogen-Activated Protein Kinases, Signal Transduction, ras Proteins, RASopathy, Ras, MAPK, cancer, rare disorders, clinical trials, experimental models, Ras/MAPK, Clinical Sciences, Clinical sciences
Abstract

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. © 2016 Wiley Periodicals, Inc.

Published
2016

11. The third international meeting on genetic disorders in the RAS/MAPK pathway: Towards a therapeutic approach

Author

Korf, Bruce, Ahmadian, Reza, Allanson, Judith, Aoki, Yoko, Bakker, Annette, Wright, Emma Burkitt, Denger, Brian, Elgersma, Ype, Gelb, Bruce D, Gripp, Karen W, Kerr, Bronwyn, Kontaridis, Maria, Lazaro, Conxi, Linardic, Corinne, Lozano, Reymundo, MacRae, Calum A, Messiaen, Ludwine, Mulero-Navarro, Sonia, Neel, Benjamin, Plotkin, Scott, Rauen, Katherine A, Roberts, Amy, Silva, Alcino J, Sittampalam, Sitta G, Zhang, Chao, and Schoyer, Lisa

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Orphan Drug, Cancer, Rare Diseases, Genetic Diseases, Inborn, Humans, MAP Kinase Signaling System, ras Proteins, Ras, neurofibromatosis, noonan syndrome, costello syndrome, cardio-facio-cutaneous syndrome, Cardio-facio-cutaneous syndrome, Costello syndrome, Noonan syndrome, Clinical Sciences, Clinical sciences
Abstract

"The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion.

Published
2015

12. Spatially clustering de novo variants in CYFIP2, encoding the cytoplasmic FMRP interacting protein 2, cause intellectual disability and seizures

Author

Zweier, Markus, Begemann, Anaïs, McWalter, Kirsty, Cho, Megan T., Abela, Lucia, Banka, Siddharth, Behring, Bettina, Berger, Andrea, Brown, Chester W., Carneiro, Maryline, Chen, Jiani, Cooper, Gregory M., Deciphering Developmental Disorders (DDD) Study, Finnila, Candice R., Guillen Sacoto, Maria J., Henderson, Alex, Hüffmeier, Ulrike, Joset, Pascal, Kerr, Bronwyn, Lesca, Gaetan, Leszinski, Gloria S., McDermott, John Henry, Meltzer, Meira R., Monaghan, Kristin G., Mostafavi, Roya, Õunap, Katrin, Plecko, Barbara, Powis, Zöe, Purcarin, Gabriela, Reimand, Tiia, Riedhammer, Korbinian M., Schreiber, John M., Sirsi, Deepa, Wierenga, Klaas J., Wojcik, Monica H., Papuc, Sorina M., Steindl, Katharina, Sticht, Heinrich, and Rauch, Anita

Published
2019
Full Text
View/download PDF

13. Biallelic variants in PIGN cause Fryns syndrome, multiple congenital anomalies-hypotonia-seizures syndrome, and neurologic phenotypes: A genotype–phenotype correlation study

Author

Loong, Lucy, primary, Tardivo, Agostina, additional, Knaus, Alexej, additional, Hashim, Mona, additional, Pagnamenta, Alistair T., additional, Alt, Kerstin, additional, Böhrer-Rabel, Helena, additional, Caro-Llopis, Alfonso, additional, Cole, Trevor, additional, Distelmaier, Felix, additional, Edery, Patrick, additional, Ferreira, Carlos R., additional, Jezela-Stanek, Aleksandra, additional, Kerr, Bronwyn, additional, Kluger, Gerhard, additional, Krawitz, Peter M., additional, Kuhn, Marius, additional, Lemke, Johannes R., additional, Lesca, Gaetan, additional, Lynch, Sally Ann, additional, Martinez, Francisco, additional, Maxton, Caroline, additional, Mierzewska, Hanna, additional, Monfort, Sandra, additional, Nicolai, Joost, additional, Orellana, Carmen, additional, Pal, Deb K., additional, Płoski, Rafał, additional, Quarrell, Oliver W., additional, Rosello, Monica, additional, Rydzanicz, Małgorzata, additional, Sabir, Ataf, additional, Śmigiel, Robert, additional, Stegmann, Alexander P.A., additional, Stewart, Helen, additional, Stumpel, Constance, additional, Szczepanik, Elżbieta, additional, Tzschach, Andreas, additional, Wolfe, Lynne, additional, Taylor, Jenny C., additional, Murakami, Yoshiko, additional, Kinoshita, Taroh, additional, Bayat, Allan, additional, and Kini, Usha, additional

Published
2023
Full Text
View/download PDF

14. Oculo-auriculo-vertebral spectrum: Clinical and molecular analysis of 51 patients

Author

Beleza-Meireles, Ana, Hart, Rachel, Clayton-Smith, Jill, Oliveira, Renata, Reis, Cláudia Falcão, Venâncio, Margarida, Ramos, Fabiana, Sá, Joaquim, Ramos, Lina, Cunha, Elizabete, Pires, Luís Miguel, Carreira, Isabel Marques, Scholey, Rachel, Wright, Ronnie, Urquhart, Jill E., Briggs, Tracy A., Kerr, Bronwyn, Kingston, Helen, Metcalfe, Kay, Donnai, Dian, Newman, William G., Saraiva, Jorge Manuel, and Tassabehji, May

Published
2015
Full Text
View/download PDF

15. The genetic basis of DOORS syndrome: an exome-sequencing study

Author

Campeau, Philippe M, Kasperaviciute, Dalia, Lu, James T, Burrage, Lindsay C, Kim, Choel, Hori, Mutsuki, Powell, Berkley R, Stewart, Fiona, Félix, Têmis Maria, van den Ende, Jenneke, Wisniewska, Marzena, Kayserili, Hülya, Rump, Patrick, Nampoothiri, Sheela, Aftimos, Salim, Mey, Antje, Nair, Lal D V, Begleiter, Michael L, De Bie, Isabelle, Meenakshi, Girish, Murray, Mitzi L, Repetto, Gabriela M, Golabi, Mahin, Blair, Edward, Male, Alison, Giuliano, Fabienne, Kariminejad, Ariana, Newman, William G, Bhaskar, Sanjeev S, Dickerson, Jonathan E, Kerr, Bronwyn, Banka, Siddharth, Giltay, Jacques C, Wieczorek, Dagmar, Tostevin, Anna, Wiszniewska, Joanna, Cheung, Sau Wai, Hennekam, Raoul C, Gibbs, Richard A, Lee, Brendan H, and Sisodiya, Sanjay M

Published
2014
Full Text
View/download PDF

17. Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes

Author

de Kovel, Carolien G. F., Syrbe, Steffen, Brilstra, Eva H., Verbeek, Nienke, Kerr, Bronwyn, Dubbs, Holly, Bayat, Allan, Desai, Sonal, Naidu, Sakkubai, Srivastava, Siddharth, Cagaylan, Hande, Yis, Uluc, Saunders, Carol, Rook, Martin, Plugge, Susanna, Muhle, Hiltrud, Afawi, Zaid, Klein, Karl-Martin, Jayaraman, Vijayakumar, Rajagopalan, Ramakrishnan, Goldberg, Ethan, Marsh, Eric, Kessler, Sudha, Bergqvist, Christina, Conlin, Laura K., Krok, Bryan L., Thiffault, Isabelle, Pendziwiat, Manuela, Helbig, Ingo, Polster, Tilman, Borggraefe, Ingo, Lemke, Johannes R., van den Boogaardt, Marie-José, Møller, Rikke S., and Koeleman, Bobby P. C.

Published
2017
Full Text
View/download PDF

18. Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline

Author

Giannoulatou, Eleni, McVean, Gilean, Taylor, Indira B., McGowan, Simon J., Maher, Geoffrey J., Iqbal, Zamin, Pfeifer, Susanne P., Turner, Isaac, Wright, Emma M. M. Burkitt, Shorto, Jennifer, Itani, Aysha, Turner, Karen, Gregory, Lorna, Buck, David, Meyts, Ewa Rajpert-De, Looijenga, Leendert H. J., Kerr, Bronwyn, Wilkie, Andrew O. M., and Goriely, Anne

Published
2013

19. Prevalence and architecture of de novo mutations in developmental disorders

Author

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.

Published
2017
Full Text
View/download PDF

20. Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease

Author

Lennon, Rachel, Stuart, Helen M., Bierzynska, Agnieszka, Randles, Michael J., Kerr, Bronwyn, Hillman, Katherine A., Batra, Gauri, Campbell, Joanna, Storey, Helen, Flinter, Frances A., Koziell, Ania, Welsh, Gavin I., Saleem, Moin A., Webb, Nicholas J. A., and Woolf, Adrian S.

Subjects
Teenage boys -- Research -- Health aspects, Gene mutation -- Research, Transmission electron microscopes -- Research -- Usage, Health
Abstract

Background Mutations in podocyte and basement membrane genes are associated with a growing spectrum of glomerular disease affecting adults and children. Investigation of familial cases has helped to build understanding of both normal physiology and disease. Methods We investigated a consanguineous family with a wide clinical phenotype of glomerular disease using clinical, histological, and new genetic studies. Results We report striking variability in severity of nephropathy within an X-linked Alport syndrome (XLAS) family. Four siblings each carried a mutant COL4A5 allele, p.(Gly953Val) and p.(Gly1033Arg). Two boys had signs limited to hematuria and mild/moderate proteinuria. In striking contrast, a sister presented with end-stage renal disease (ESRD) at 8 years of age and an infant brother presented with nephrotic syndrome, progressing to ESRD by 3 years of age. Both were subsequently found to have homozygous variants in MYO1E, p.(Lys118Glu) and p.(Thr876Arg). MYO1E is a gene implicated in focal segmental glomerulosclerosis and it encodes a podocyte-expressed non-muscle myosin. Bioinformatic modeling demonstrated that the collagen IV-alpha3,4,5 extracellular network connected via known protein-protein interactions to intracellular myosin 1E. Conclusions COL4A5 and MYO1E mutations may summate to perturb common signaling pathways, resulting in more severe disease than anticipated independently. We suggest screening for MYO1E and other non-COL4 'podocyte gene' mutations in XLAS when clinical nephropathy is more severe than expected for an individual's age and sex., Author(s): Rachel Lennon[sup.1] [sup.2] [sup.3] , Helen M. Stuart[sup.4] , Agnieszka Bierzynska[sup.5] , Michael J. Randles[sup.1] [sup.2] , Bronwyn Kerr[sup.4] , Katherine A. Hillman[sup.6] , Gauri Batra[sup.7] , Joanna Campbell[sup.8] [...]

Published
2015
Full Text
View/download PDF

22. Biallelic variants in PIGNcause Fryns syndrome, multiple congenital anomalies-hypotonia-seizures syndrome, and neurologic phenotypes: A genotype–phenotype correlation study

Author

Loong, Lucy, Tardivo, Agostina, Knaus, Alexej, Hashim, Mona, Pagnamenta, Alistair T., Alt, Kerstin, Böhrer-Rabel, Helena, Caro-Llopis, Alfonso, Cole, Trevor, Distelmaier, Felix, Edery, Patrick, Ferreira, Carlos R., Jezela-Stanek, Aleksandra, Kerr, Bronwyn, Kluger, Gerhard, Krawitz, Peter M., Kuhn, Marius, Lemke, Johannes R., Lesca, Gaetan, Lynch, Sally Ann, Martinez, Francisco, Maxton, Caroline, Mierzewska, Hanna, Monfort, Sandra, Nicolai, Joost, Orellana, Carmen, Pal, Deb K., Płoski, Rafał, Quarrell, Oliver W., Rosello, Monica, Rydzanicz, Małgorzata, Sabir, Ataf, Śmigiel, Robert, Stegmann, Alexander P.A., Stewart, Helen, Stumpel, Constance, Szczepanik, Elżbieta, Tzschach, Andreas, Wolfe, Lynne, Taylor, Jenny C., Murakami, Yoshiko, Kinoshita, Taroh, Bayat, Allan, and Kini, Usha

Abstract

Biallelic PIGNvariants have been described in Fryns syndrome, multiple congenital anomalies-hypotonia-seizure syndrome (MCAHS), and neurologic phenotypes. The full spectrum of clinical manifestations in relation to the genotypes is yet to be reported.

Published
2023
Full Text
View/download PDF

23. Author Correction: CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language

Author

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

24. Leri’s pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis

Author

Banka, Siddharth, Cain, Stuart A, Carim, Sabrya, Daly, Sarah B, Urquhart, Jill E, Erdem, Günhan, Harris, Jade, Bottomley, Michelle, Donnai, Dian, Kerr, Bronwyn, Kingston, Helen, Superti-Furga, Andreas, Unger, Sheila, Ennis, Holly, Worthington, Jane, Herrick, Ariane L, Merry, Catherine L R, Yue, Wyatt W, Kielty, Cay M, and Newman, William G

Published
2015
Full Text
View/download PDF

25. A Study of the Clinical and Radiological Features in a Cohort of 93 Patients with a COL2A1 Mutation Causing Spondyloepiphyseal Dysplasia Congenita or a Related Phenotype

Author

Terhal, Paulien A., Nievelstein, Rutger Jan A. J., Verver, Eva J. J., Topsakal, Vedat, van Dommelen, Paula, Hoornaert, Kristien, Le Merrer, Martine, Zankl, Andreas, Simon, Marleen E. H., Smithson, Sarah F., Marcelis, Carlo, Kerr, Bronwyn, Clayton-Smith, Jill, Kinning, Esther, Mansour, Sahar, Elmslie, Frances, Goodwin, Linda, van der Hout, Annemarie H., Veenstra-Knol, Hermine E., Herkert, Johanna C., Lund, Allan M., Hennekam, Raoul C. M., Mégarbané, André, Lees, Melissa M., Wilson, Louise C., Male, Alison, Hurst, Jane, Alanay, Yasemin, Annerén, Göran, Betz, Regina C., Bongers, Ernie M. H. F., Cormier-Daire, Valerie, Dieux, Anne, David, Albert, Elting, Mariet W., van den Ende, Jenneke, Green, Andrew, van Hagen, Johanna M., Hertel, Niels Thomas, Holder-Espinasse, Muriel, den Hollander, Nicolette, Homfray, Tessa, Hove, Hanne D., Price, Susan, Raas-Rothschild, Annick, Rohrbach, Marianne, Schroeter, Barbara, Suri, Mohnish, Thompson, Elizabeth M., Tobias, Edward S., Toutain, Annick, Vreeburg, Maaike, Wakeling, Emma, Knoers, Nine V., Coucke, Paul, and Mortier, Geert R.

Published
2015
Full Text
View/download PDF

26. Recent developments in neurofibromatoses and RASopathies: Management, diagnosis and current and future therapeutic avenues

Author

Rauen, Katherine A., Huson, Susan M., Burkitt-Wright, Emma, Evans, Gareth D., Farschtschi, Said, Ferner, Rosalie E., Gutmann, David H., Hanemann, Oliver C., Kerr, Bronwyn, Legius, Eric, Parada, Luis F., Patton, Michael, Peltonen, Juha, Ratner, Nancy, Riccardi, Vincent M., van der Vaart, Thijs, Vikkula, Miikka, Viskochil, David H., Zenker, Martin, and Upadhyaya, Meena

Published
2015
Full Text
View/download PDF

27. The contribution of X-linked coding variation to severe developmental disorders

Author

Martin, Hilary C., Gardner, Eugene J., Samocha, Kaitlin E., Kaplanis, Joanna, Akawi, Nadia, Sifrim, Alejandro, Eberhardt, Ruth Y., Tavares, Ana Lisa Taylor, Neville, Matthew D. C., Niemi, Mari E. K., Gallone, Giuseppe, McRae, Jeremy, Wright, Caroline F., FitzPatrick, David R., Firth, Helen V., Hurles, Matthew E., 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, Kumar, V.K.Ajith, 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, Martin, Hilary C. [0000-0002-4454-9084], Gardner, Eugene J. [0000-0001-9671-1533], Samocha, Kaitlin E. [0000-0002-1704-3352], Eberhardt, Ruth Y. [0000-0001-6152-1369], Tavares, Ana Lisa Taylor [0000-0001-7089-0502], Neville, Matthew D. C. [0000-0001-5816-7936], Niemi, Mari E. K. [0000-0003-0696-6175], Wright, Caroline F. [0000-0003-2958-5076], Hurles, Matthew E. [0000-0002-2333-7015], and Apollo - University of Cambridge Repository

Subjects
631/208/366, 49/23, article, 631/208/1516, 631/208/205
Abstract

Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders.

Published
2021
Full Text
View/download PDF

28. 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
Full Text
View/download PDF

29. Personalised virtual gene panels reduce interpretation workload and maintain diagnostic rates of proband-only clinical exome sequencing for rare disorders

Author

Molina-Ramírez, Leslie Patricia, primary, Kyle, Claire, additional, Ellingford, Jamie M, additional, Wright, Ronnie, additional, Taylor, Algy, additional, Bhaskar, Sanjeev S, additional, Campbell, Christopher, additional, Jackson, Harriet, additional, Fairclough, Adele, additional, Rousseau, Abigail, additional, Burghel, George J, additional, Dutton, Laura, additional, Banka, Siddharth, additional, Briggs, Tracy A, additional, Clayton-Smith, Jill, additional, Douzgou, Sofia, additional, Jones, Elizabeth A, additional, Kingston, Helen M, additional, Kerr, Bronwyn, additional, Ealing, John, additional, Somarathi, Suresh, additional, Chandler, Kate E, additional, Stuart, Helen M, additional, Burkitt-Wright, Emma MM, additional, Newman, William G, additional, Bruce, Iain A, additional, Black, Graeme C, additional, and Gokhale, David, additional

Published
2021
Full Text
View/download PDF

30. RAS-MAPK pathway disorders: important causes of congenital heart disease, feeling difficulties, developmental delay and short stature

Author

Burkitt Wright, Emma M.M. and Kerr, Bronwyn

Subjects
Ingestion disorders -- Genetic aspects, Ingestion disorders -- Causes of, Developmental delay -- Genetic aspects, Developmental delay -- Causes of, Stature, Short -- Genetic aspects, Stature, Short -- Causes of, Ras genes -- Physiological aspects, Ras genes -- Abnormalities, Mitogen-activated protein kinases -- Genetic aspects, Mitogen-activated protein kinases -- Physiological aspects, Congenital heart disease -- Genetic aspects, Congenital heart disease -- Causes of
Published
2010

31. Mutations in HPSE2 cause urofacial syndrome

Author

Daly, Sarah B., Urquhart, Jill E., Hilton, Emma, McKenzie, Edward A., Kammerer, Richard A., Lewis, Malcolm, Kerr, Bronwyn, Stuart, Helen, Donnai, Dian, Long, David A., Burgu, Berk, Aydogdu, Ozgu, Derbent, Murat, Garcia-Minaur, Sixto, Reardon, Willie, Gener, Blanca, Shalev, Stavit, Smith, Rupert, Woolf, Adrian S., Black, Graeme C., and Newman, William G.

Subjects
Chromosome deletion -- Analysis, Facial expression -- Genetic aspects, Gene mutations -- Analysis, Single nucleotide polymorphisms -- Research, Urologic diseases -- Genetic aspects, Biological sciences
Abstract

Several analyses are conducted to explain the causes of the urofacial syndrome, a rare autosomal recessive disorder. The study is shown to be of extreme significance for understanding the lower renal tract malformations and voiding dysfunction in humans.

Published
2010

32. Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis

Author

Flex, Elisabetta, Jaiswal, Mamta, Pantaleoni, Francesca, Martinelli, Simone, Strullu, Marion, Fansa, Eyad K., Caye, Aurélie, De Luca, Alessandro, Lepri, Francesca, Dvorsky, Radovan, Pannone, Luca, Paolacci, Stefano, Zhang, Si-Cai, Fodale, Valentina, Bocchinfuso, Gianfranco, Rossi, Cesare, Burkitt-Wright, Emma M.M., Farrotti, Andrea, Stellacci, Emilia, Cecchetti, Serena, Ferese, Rosangela, Bottero, Lisabianca, Castro, Silvana, Fenneteau, Odile, Brethon, Benoît, Sanchez, Massimo, Roberts, Amy E., Yntema, Helger G., Van Der Burgt, Ineke, Cianci, Paola, Bondeson, Marie-Louise, Cristina Digilio, Maria, Zampino, Giuseppe, Kerr, Bronwyn, Aoki, Yoko, Loh, Mignon L., Palleschi, Antonio, Di Schiavi, Elia, Carè, Alessandra, Selicorni, Angelo, Dallapiccola, Bruno, Cirstea, Ion C., Stella, Lorenzo, Zenker, Martin, Gelb, Bruce D., Cavé, Hélène, Ahmadian, Mohammad R., and Tartaglia, Marco

Published
2014
Full Text
View/download PDF

33. SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Author

Radio, Francesca Clementina, primary, Pang, Kaifang, additional, Ciolfi, Andrea, additional, Levy, Michael A., additional, Hernández-García, Andrés, additional, Pedace, Lucia, additional, Pantaleoni, Francesca, additional, Liu, Zhandong, additional, de Boer, Elke, additional, Jackson, Adam, additional, Bruselles, Alessandro, additional, McConkey, Haley, additional, Stellacci, Emilia, additional, Lo Cicero, Stefania, additional, Motta, Marialetizia, additional, Carrozzo, Rosalba, additional, Dentici, Maria Lisa, additional, McWalter, Kirsty, additional, Desai, Megha, additional, Monaghan, Kristin G., additional, Telegrafi, Aida, additional, Philippe, Christophe, additional, Vitobello, Antonio, additional, Au, Margaret, additional, Grand, Katheryn, additional, Sanchez-Lara, Pedro A., additional, Baez, Joanne, additional, Lindstrom, Kristin, additional, Kulch, Peggy, additional, Sebastian, Jessica, additional, Madan-Khetarpal, Suneeta, additional, Roadhouse, Chelsea, additional, MacKenzie, Jennifer J., additional, Monteleone, Berrin, additional, Saunders, Carol J., additional, Jean Cuevas, July K., additional, Cross, Laura, additional, Zhou, Dihong, additional, Hartley, Taila, additional, Sawyer, Sarah L., additional, Monteiro, Fabíola Paoli, additional, Secches, Tania Vertemati, additional, Kok, Fernando, additional, Schultz-Rogers, Laura E., additional, Macke, Erica L., additional, Morava, Eva, additional, Klee, Eric W., additional, Kemppainen, Jennifer, additional, Iascone, Maria, additional, Selicorni, Angelo, additional, Tenconi, Romano, additional, Amor, David J., additional, Pais, Lynn, additional, Gallacher, Lyndon, additional, Turnpenny, Peter D., additional, Stals, Karen, additional, Ellard, Sian, additional, Cabet, Sara, additional, Lesca, Gaetan, additional, Pascal, Joset, additional, Steindl, Katharina, additional, Ravid, Sarit, additional, Weiss, Karin, additional, Castle, Alison M.R., additional, Carter, Melissa T., additional, Kalsner, Louisa, additional, de Vries, Bert B.A., additional, van Bon, Bregje W., additional, Wevers, Marijke R., additional, Pfundt, Rolph, additional, Stegmann, Alexander P.A., additional, Kerr, Bronwyn, additional, Kingston, Helen M., additional, Chandler, Kate E., additional, Sheehan, Willow, additional, Elias, Abdallah F., additional, Shinde, Deepali N., additional, Towne, Meghan C., additional, Robin, Nathaniel H., additional, Goodloe, Dana, additional, Vanderver, Adeline, additional, Sherbini, Omar, additional, Bluske, Krista, additional, Hagelstrom, R. Tanner, additional, Zanus, Caterina, additional, Faletra, Flavio, additional, Musante, Luciana, additional, Kurtz-Nelson, Evangeline C., additional, Earl, Rachel K., additional, Anderlid, Britt-Marie, additional, Morin, Gilles, additional, van Slegtenhorst, Marjon, additional, Diderich, Karin E.M., additional, Brooks, Alice S., additional, Gribnau, Joost, additional, Boers, Ruben G., additional, Finestra, Teresa Robert, additional, Carter, Lauren B., additional, Rauch, Anita, additional, Gasparini, Paolo, additional, Boycott, Kym M., additional, Barakat, Tahsin Stefan, additional, Graham, John M., additional, Faivre, Laurence, additional, Banka, Siddharth, additional, Wang, Tianyun, additional, Eichler, Evan E., additional, Priolo, Manuela, additional, Dallapiccola, Bruno, additional, Vissers, Lisenka E.L.M., additional, Sadikovic, Bekim, additional, Scott, Daryl A., additional, Holder, Jimmy Lloyd, additional, and Tartaglia, Marco, additional

Published
2021
Full Text
View/download PDF

35. Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause x-linked mental retardation associated with a marfanoid habitus

Author

Raymond, F. Lucy, Tarpey, Patrick S., Edkins, Sarah, Tofts, Calli, O'Meara, Sarah, Shaw, Marie, Schwartz, Charles E., Teague, Jon, Butler, Adam, Stevens, Claire, Barthorpe, Syd, Buck, Gemma, Boyle, Jackie, Bobrow, Martin, Cole, Jennifer, Dicks, Ed, Gray, Kristian, Halliday, Kelly, Hills, Katy, Hinton, Jonathon, Kerr, Bronwyn, Wooster, Richard, Jones, David, Menzies, Andrew, Perry, Janet, Raine, Keiran, Shepherd, Rebecca, Turner, Gillian, Easton, Douglas F., Futreal, P. Andrew, Small, Alexandra, Varian, Jennifer, Widaa, Sara, Mallya, Uma, Jenny Moon, Ying Luo, Quarrell, Oliver, Cole, Trevor, Gecz, Jozef, and Stratton, Michael R.

Subjects
Gene mutations -- Research, Fragile X syndrome -- Genetic aspects, Fragile X syndrome -- Research, Marfan syndrome -- Risk factors, Biological sciences
Abstract

One frameshift mutation, one splice-site mutation and two missense mutations are identified in highly conserved residues in ZDHHC9 at Xq26.1 in 4 of 250 families with X-linked mental retardation (XLMR). It is found that in three of the families, the mental retardation phenotype is associated with a Marfanoid habitus, however none of the affected individuals meets the Ghent criteria for Marfan syndrome.

Published
2007

42. Mutation-based growth charts for SEDC and other COL2A1 related dysplasias

Author

Terhal, Paulien A., van Dommelen, Paula, Le Merrer, Martine, Zankl, Andreas, Simon, Marleen E.H., Smithson, Sarah F., Marcelis, Carlo, Kerr, Bronwyn, Kinning, Esther, Mansour, Sahar, Hennekam, Raoul C.M., van der Hout, Annemarie H., Cormier-Daire, Valerie, Lund, Allan M., Goodwin, Linda, Mégarbané, André, Lees, Melissa, Betz, Regina C., Tobias, Edward S., Coucke, Paul, and Mortier, Geert R.

Published
2012
Full Text
View/download PDF

45. Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

Author

Lin, Angela E., Alexander, Mark E., Colan, Steven D., Kerr, Bronwyn, Rauen, Katherine A., Noonan, Jacqueline, Baffa, Jeanne, Hopkins, Elizabeth, Sol-Church, Katia, Limongelli, Giuseppe, Digilio, Maria Christina, Marino, Bruno, Innes, Micheil A., Aoki, Yoko, Silberbach, Michael, Delrue, Marie-Ange, White, Susan M., Hamilton, Robert M., OʼConnor, William, Grossfeld, Paul D., Smoot, Leslie B., Padera, Robert F., and Gripp, Karen W.

Published
2011
Full Text
View/download PDF

47. The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families

Author

Grocock, Christopher J, Rebours, Vinciane, Delhaye, Myriam N, Andrén-Sandberg, Åke, Weiss, Frank Ulrich, Mountford, Roger, Harcus, Matthew J, Niemczyck, Edyta, Vitone, Louis J, Dodd, Susanna, Jørgensen, Maiken Thyregod, Ammann, Rudolf W, Schaffalitzky de Muckadell, Ove, Butler, Jane V, Burgess, Phillip, Kerr, Bronwyn, Charnley, Richard, Sutton, Robert, Raraty, Michael G, Devière, Jacques, Whitcomb, David C, Neoptolemos, John P, Lévy, Philippe, Lerch, Markus M, and Greenhalf, William

Published
2010
Full Text
View/download PDF

48. Brachydactyly type B: clinical description, genetic mapping to chromosome 9q, and evidence for a shared ancestral mutation

Author

Gong, Yaoqin, Chitayat, David, Kerr, Bronwyn, Chen, Taiping, Babul-Hirji, Riyana, Pal, Adatiya, Reiss, Michael, and Warman, Matthew L.

Subjects
Genetic disorders -- Research, Chromosome mapping -- Usage, Fingernails -- Abnormalities, Hand -- Abnormalities, Foot -- Abnormalities, Biological sciences
Abstract

Autosomal dominant brachydactyly type B (BDB), which has been studied in two families of English ancestry and linked to chromosome 9q, seems to have a common founder for involved families with that ethnic background. BDB is characterized by aplasia of the nails with rudimentary or missing distal and middle phalanges, sometimes asymmetrical.

Published
1999

50. Molecular aspects, clinical aspects and possible treatment modalities for Costello syndrome: Proceedings from the 1st International Costello Syndrome Research Symposium 2007

Author

Rauen, Katherine A., Hefner, Erin, Carrillo, Kristin, Taylor, Jill, Messier, Laure, Aoki, Yoko, Gripp, Karen W., Matsubara, Yoichi, Proud, Virginia K., Hammond, Peter, Allanson, Judith E., Delrue, Marie-Ange, Axelrad, Marni E., Lin, Angela E., Doyle, Daniel A., Kerr, Bronwyn, Carey, John C., McCormick, Frank, Silva, Alcino J., Kieran, Mark W., Hinek, Aleksander, Nguyen, Tan T., and Schoyer, Lisa

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results