16 results on '"Jolly, Lachlan A"'
Search Results
2. Endogenous protein interactomes resolved through immunoprecipitation-coupled quantitative proteomics in cell lines
- Author
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Kumar, Raman, primary, Kamath, Karthik S., additional, Carroll, Luke, additional, Hoffmann, Peter, additional, Gecz, Jozef, additional, and Jolly, Lachlan A., additional
- Published
- 2022
- Full Text
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3. Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants
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Kayumi, Sayaka, primary, Pérez-Jurado, Luis A., additional, Palomares, María, additional, Rangu, Sneha, additional, Sheppard, Sarah E., additional, Chung, Wendy K., additional, Kruer, Michael C., additional, Kharbanda, Mira, additional, Amor, David J., additional, McGillivray, George, additional, Cohen, Julie S., additional, García-Miñaúr, Sixto, additional, van Eyk, Clare L., additional, Harper, Kelly, additional, Jolly, Lachlan A., additional, Webber, Dani L., additional, Barnett, Christopher P., additional, Santos-Simarro, Fernando, additional, Pacio-Míguez, Marta, additional, Pozo, Angela del, additional, Bakhtiari, Somayeh, additional, Deardorff, Matthew, additional, Dubbs, Holly A., additional, Izumi, Kosuke, additional, Grand, Katheryn, additional, Gray, Christopher, additional, Mark, Paul R., additional, Bhoj, Elizabeth J., additional, Li, Dong, additional, Ortiz-Gonzalez, Xilma R., additional, Keena, Beth, additional, Zackai, Elaine H., additional, Goldberg, Ethan M., additional, Perez de Nanclares, Guiomar, additional, Pereda, Arrate, additional, Llano-Rivas, Isabel, additional, Arroyo, Ignacio, additional, Fernández-Cuesta, María Ángeles, additional, Thauvin-Robinet, Christel, additional, Faivre, Laurence, additional, Garde, Aurore, additional, Mazel, Benoit, additional, Bruel, Ange-Line, additional, Tress, Michael L., additional, Brilstra, Eva, additional, Fine, Amena Smith, additional, Crompton, Kylie E., additional, Stegmann, Alexander P.A., additional, Sinnema, Margje, additional, Stevens, Servi C.J., additional, Nicolai, Joost, additional, Lesca, Gaetan, additional, Lion-François, Laurence, additional, Haye, Damien, additional, Chatron, Nicolas, additional, Piton, Amelie, additional, Nizon, Mathilde, additional, Cogne, Benjamin, additional, Srivastava, Siddharth, additional, Bassetti, Jennifer, additional, Muss, Candace, additional, Gripp, Karen W., additional, Procopio, Rebecca A., additional, Millan, Francisca, additional, Morrow, Michelle M., additional, Assaf, Melissa, additional, Moreno-De-Luca, Andres, additional, Joss, Shelagh, additional, Hamilton, Mark J., additional, Bertoli, Marta, additional, Foulds, Nicola, additional, McKee, Shane, additional, MacLennan, Alastair H., additional, Gecz, Jozef, additional, and Corbett, Mark A., additional
- Published
- 2022
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4. The DUB Club: Deubiquitinating Enzymes and Neurodevelopmental Disorders
- Author
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Jolly, Lachlan A., primary, Kumar, Raman, additional, Penzes, Peter, additional, Piper, Michael, additional, and Gecz, Jozef, additional
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- 2022
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5. Impaired neural differentiation of MPS IIIA patient induced pluripotent stem cell-derived neural progenitor cells
- Author
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Lehmann, Rebecca J., primary, Jolly, Lachlan A., additional, Johnson, Brett V., additional, Lord, Megan S., additional, Kim, Ha Na, additional, Saville, Jennifer T., additional, Fuller, Maria, additional, Byers, Sharon, additional, and Derrick-Roberts, Ainslie L.K., additional
- Published
- 2021
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6. Usp9X Controls Ankyrin-Repeat Domain Protein Homeostasis during Dendritic Spine Development
- Author
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Yoon, Sehyoun, primary, Parnell, Euan, additional, Kasherman, Maria, additional, Forrest, Marc P., additional, Myczek, Kristoffer, additional, Premarathne, Susitha, additional, Sanchez Vega, Michelle C., additional, Piper, Michael, additional, Burne, Thomas H.J., additional, Jolly, Lachlan A., additional, Wood, Stephen A., additional, and Penzes, Peter, additional
- Published
- 2020
- Full Text
- View/download PDF
7. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling
- Author
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Johnson, Brett V., primary, Kumar, Raman, additional, Oishi, Sabrina, additional, Alexander, Suzy, additional, Kasherman, Maria, additional, Vega, Michelle Sanchez, additional, Ivancevic, Atma, additional, Gardner, Alison, additional, Domingo, Deepti, additional, Corbett, Mark, additional, Parnell, Euan, additional, Yoon, Sehyoun, additional, Oh, Tracey, additional, Lines, Matthew, additional, Lefroy, Henrietta, additional, Kini, Usha, additional, Van Allen, Margot, additional, Grønborg, Sabine, additional, Mercier, Sandra, additional, Küry, Sébastien, additional, Bézieau, Stéphane, additional, Pasquier, Laurent, additional, Raynaud, Martine, additional, Afenjar, Alexandra, additional, Billette de Villemeur, Thierry, additional, Keren, Boris, additional, Désir, Julie, additional, Van Maldergem, Lionel, additional, Marangoni, Martina, additional, Dikow, Nicola, additional, Koolen, David A., additional, VanHasselt, Peter M., additional, Weiss, Marjan, additional, Zwijnenburg, Petra, additional, Sa, Joaquim, additional, Reis, Claudia Falcao, additional, López-Otín, Carlos, additional, Santiago-Fernández, Olaya, additional, Fernández-Jaén, Alberto, additional, Rauch, Anita, additional, Steindl, Katharina, additional, Joset, Pascal, additional, Goldstein, Amy, additional, Madan-Khetarpal, Suneeta, additional, Infante, Elena, additional, Zackai, Elaine, additional, Mcdougall, Carey, additional, Narayanan, Vinodh, additional, Ramsey, Keri, additional, Mercimek-Andrews, Saadet, additional, Pena, Loren, additional, Shashi, Vandana, additional, Schoch, Kelly, additional, Sullivan, Jennifer A., additional, Pinto e Vairo, Filippo, additional, Pichurin, Pavel N., additional, Ewing, Sarah A., additional, Barnett, Sarah S., additional, Klee, Eric W., additional, Perry, M. Scott, additional, Koenig, Mary Kay, additional, Keegan, Catherine E., additional, Schuette, Jane L., additional, Asher, Stephanie, additional, Perilla-Young, Yezmin, additional, Smith, Laurie D., additional, Rosenfeld, Jill A., additional, Bhoj, Elizabeth, additional, Kaplan, Paige, additional, Li, Dong, additional, Oegema, Renske, additional, van Binsbergen, Ellen, additional, van der Zwaag, Bert, additional, Smeland, Marie Falkenberg, additional, Cutcutache, Ioana, additional, Page, Matthew, additional, Armstrong, Martin, additional, Lin, Angela E., additional, Steeves, Marcie A., additional, Hollander, Nicolette den, additional, Hoffer, Mariëtte J.V., additional, Reijnders, Margot R.F., additional, Demirdas, Serwet, additional, Koboldt, Daniel C., additional, Bartholomew, Dennis, additional, Mosher, Theresa Mihalic, additional, Hickey, Scott E., additional, Shieh, Christine, additional, Sanchez-Lara, Pedro A., additional, Graham, John M., additional, Tezcan, Kamer, additional, Schaefer, G.B., additional, Danylchuk, Noelle R., additional, Asamoah, Alexander, additional, Jackson, Kelly E., additional, Yachelevich, Naomi, additional, Au, Margaret, additional, Pérez-Jurado, Luis A., additional, Kleefstra, Tjitske, additional, Penzes, Peter, additional, Wood, Stephen A., additional, Burne, Thomas, additional, Pierson, Tyler Mark, additional, Piper, Michael, additional, Gécz, Jozef, additional, Jolly, Lachlan A., additional, Acosta, Maria T., additional, Adams, David R., additional, Aday, Aaron, additional, Alejandro, Mercedes E., additional, Allard, Patrick, additional, Ashley, Euan A., additional, Azamian, Mahshid S., additional, Bacino, Carlos A., additional, Bademci, Guney, additional, Baker, Eva, additional, Balasubramanyam, Ashok, additional, Baldridge, Dustin, additional, Barbouth, Deborah, additional, Batzli, Gabriel F., additional, Beggs, Alan H., additional, Bellen, Hugo J., additional, Bernstein, Jonathan A., additional, Berry, Gerard T., additional, Bican, Anna, additional, Bick, David P., additional, Birch, Camille L., additional, Bivona, Stephanie, additional, Bonnenmann, Carsten, additional, Bonner, Devon, additional, Boone, Braden E., additional, Bostwick, Bret L., additional, Briere, Lauren C., additional, Brokamp, Elly, additional, Brown, Donna M., additional, Brush, Matthew, additional, Burke, Elizabeth A., additional, Burrage, Lindsay C., additional, Butte, Manish J., additional, Carrasquillo, Olveen, additional, Peter Chang, Ta Chen, additional, Chao, Hsiao-Tuan, additional, Clark, Gary D., additional, Coakley, Terra R., additional, Cobban, Laurel A., additional, Cogan, Joy D., additional, Cole, F. Sessions, additional, Colley, Heather A., additional, Cooper, Cynthia M., additional, Cope, Heidi, additional, Craigen, William J., additional, D'Souza, Precilla, additional, Dasari, Surendra, additional, Davids, Mariska, additional, Davidson, Jean M., additional, Dayal, Jyoti G., additional, Dell'Angelica, Esteban C., additional, Dhar, Shweta U., additional, Dorrani, Naghmeh, additional, Dorset, Daniel C., additional, Douine, Emilie D., additional, Draper, David D., additional, Dries, Annika M., additional, Duncan, Laura, additional, Eckstein, David J., additional, Emrick, Lisa T., additional, Eng, Christine M., additional, Enns, Gregory M., additional, Esteves, Cecilia, additional, Estwick, Tyra, additional, Fernandez, Liliana, additional, Ferreira, Carlos, additional, Fieg, Elizabeth L., additional, Fisher, Paul G., additional, Fogel, Brent L., additional, Forghani, Irman, additional, Friedman, Noah D., additional, Gahl, William A., additional, Godfrey, Rena A., additional, Goldman, Alica M., additional, Goldstein, David B., additional, Gourdine, Jean-Philippe F., additional, Grajewski, Alana, additional, Groden, Catherine A., additional, Gropman, Andrea L., additional, Haendel, Melissa, additional, Hamid, Rizwan, additional, Hanchard, Neil A., additional, High, Frances, additional, Holm, Ingrid A., additional, Hom, Jason, additional, Huang, Alden, additional, Huang, Yong, additional, Isasi, Rosario, additional, Jamal, Fariha, additional, Jiang, Yong-hui, additional, Johnston, Jean M., additional, Jones, Angela L., additional, Karaviti, Lefkothea, additional, Kelley, Emily G., additional, Koeller, David M., additional, Kohane, Isaac S., additional, Kohler, Jennefer N., additional, Krakow, Deborah, additional, Krasnewich, Donna M., additional, Korrick, Susan, additional, Koziura, Mary, additional, Krier, Joel B., additional, Kyle, Jennifer E., additional, Lalani, Seema R., additional, Lam, Byron, additional, Lanpher, Brendan C., additional, Lanza, Ian R., additional, Lau, C. Christopher, additional, Lazar, Jozef, additional, LeBlanc, Kimberly, additional, Lee, Brendan H., additional, Lee, Hane, additional, Levitt, Roy, additional, Levy, Shawn E., additional, Lewis, Richard A., additional, Lincoln, Sharyn A., additional, Liu, Pengfei, additional, Liu, Xue Zhong, additional, Loo, Sandra K., additional, Loscalzo, Joseph, additional, Maas, Richard L., additional, Macnamara, Ellen F., additional, MacRae, Calum A., additional, Maduro, Valerie V., additional, Majcherska, Marta M., additional, Malicdan, May Christine V., additional, Mamounas, Laura A., additional, Manolio, Teri A., additional, Markello, Thomas C., additional, Marom, Ronit, additional, Martin, Martin G., additional, Martínez-Agosto, Julian A., additional, Marwaha, Shruti, additional, May, Thomas, additional, McCauley, Jacob, additional, McConkie-Rosell, Allyn, additional, McCormack, Colleen E., additional, McCray, Alexa T., additional, Merker, Jason D., additional, Metz, Thomas O., additional, Might, Matthew, additional, Morava-Kozicz, Eva, additional, Moretti, Paolo M., additional, Morimoto, Marie, additional, Mulvihill, John J., additional, Murdock, David R., additional, Nath, Avi, additional, Nelson, Stan F., additional, Newberry, J. Scott, additional, Newman, John H., additional, Nicholas, Sarah K., additional, Novacic, Donna, additional, Oglesbee, Devin, additional, Orengo, James P., additional, Pak, Stephen, additional, Pallais, J. Carl, additional, Palmer, Christina GS., additional, Papp, Jeanette C., additional, Parker, Neil H., additional, Phillips, John A., additional, Posey, Jennifer E., additional, Postlethwait, John H., additional, Potocki, Lorraine, additional, Pusey, Barbara N., additional, Renteri, Genecee, additional, Reuter, Chloe M., additional, Rives, Lynette, additional, Robertson, Amy K., additional, Rodan, Lance H., additional, Rowley, Robb K., additional, Sacco, Ralph, additional, Sampson, Jacinda B., additional, Samson, Susan L., additional, Saporta, Mario, additional, Schaechter, Judy, additional, Schedl, Timothy, additional, Scott, Daryl A., additional, Shakachite, Lisa, additional, Sharma, Prashant, additional, Shields, Kathleen, additional, Shin, Jimann, additional, Signer, Rebecca, additional, Sillari, Catherine H., additional, Silverman, Edwin K., additional, Sinsheimer, Janet S., additional, Smith, Kevin S., additional, Solnica-Krezel, Lilianna, additional, Spillmann, Rebecca C., additional, Stoler, Joan M., additional, Stong, Nicholas, additional, Sweetser, David A., additional, Tamburro, Cecelia P., additional, Tan, Queenie K.-G., additional, Tekin, Mustafa, additional, Telischi, Fred, additional, Thorson, Willa, additional, Tifft, Cynthia J., additional, Toro, Camilo, additional, Tran, Alyssa A., additional, Urv, Tiina K., additional, Vogel, Tiphanie P., additional, Waggott, Daryl M., additional, Wahl, Colleen E., additional, Walley, Nicole M., additional, Walsh, Chris A., additional, Walker, Melissa, additional, Wambach, Jennifer, additional, Wan, Jijun, additional, Wang, Lee-kai, additional, Wangler, Michael F., additional, Ward, Patricia A., additional, Waters, Katrina M., additional, Webb-Robertson, Bobbie-Jo M., additional, Wegner, Daniel, additional, Westerfield, Monte, additional, Wheeler, Matthew T., additional, Wise, Anastasia L., additional, Wolfe, Lynne A., additional, Woods, Jeremy D., additional, Worthey, Elizabeth A., additional, Yamamoto, Shinya, additional, Yang, John, additional, Yoon, Amanda J., additional, Yu, Guoyun, additional, Zastrow, Diane B., additional, Zhao, Chunli, additional, Zuchner, Stephan, additional, and Gahl, William, additional
- Published
- 2020
- Full Text
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8. Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response
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Johnson, Jennifer L., primary, Stoica, Loredana, additional, Liu, Yuwei, additional, Zhu, Ping Jun, additional, Bhattacharya, Abhisek, additional, Buffington, Shelly A., additional, Huq, Redwan, additional, Eissa, N. Tony, additional, Larsson, Ola, additional, Porse, Bo T., additional, Domingo, Deepti, additional, Nawaz, Urwah, additional, Carroll, Renee, additional, Jolly, Lachlan, additional, Scerri, Tom S., additional, Kim, Hyung-Goo, additional, Brignell, Amanda, additional, Coleman, Matthew J., additional, Braden, Ruth, additional, Kini, Usha, additional, Jackson, Victoria, additional, Baxter, Anne, additional, Bahlo, Melanie, additional, Scheffer, Ingrid E., additional, Amor, David J., additional, Hildebrand, Michael S., additional, Bonnen, Penelope E., additional, Beeton, Christine, additional, Gecz, Jozef, additional, Morgan, Angela T., additional, and Costa-Mattioli, Mauro, additional
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- 2019
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9. PCDH19 regulation of neural progenitor cell differentiation suggests asynchrony of neurogenesis as a mechanism contributing to PCDH19 Girls Clustering Epilepsy
- Author
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Homan, Claire C., primary, Pederson, Stephen, additional, To, Thu-Hien, additional, Tan, Chuan, additional, Piltz, Sandra, additional, Corbett, Mark A., additional, Wolvetang, Ernst, additional, Thomas, Paul Q., additional, Jolly, Lachlan A., additional, and Gecz, Jozef, additional
- Published
- 2018
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10. De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations
- Author
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Reijnders, Margot R.F., primary, Zachariadis, Vasilios, additional, Latour, Brooke, additional, Jolly, Lachlan, additional, Mancini, Grazia M., additional, Pfundt, Rolph, additional, Wu, Ka Man, additional, van Ravenswaaij-Arts, Conny M.A., additional, Veenstra-Knol, Hermine E., additional, Anderlid, Britt-Marie M., additional, Wood, Stephen A., additional, Cheung, Sau Wai, additional, Barnicoat, Angela, additional, Probst, Frank, additional, Magoulas, Pilar, additional, Brooks, Alice S., additional, Malmgren, Helena, additional, Harila-Saari, Arja, additional, Marcelis, Carlo M., additional, Vreeburg, Maaike, additional, Hobson, Emma, additional, Sutton, V. Reid, additional, Stark, Zornitza, additional, Vogt, Julie, additional, Cooper, Nicola, additional, Lim, Jiin Ying, additional, Price, Sue, additional, Lai, Angeline Hwei Meeng, additional, Domingo, Deepti, additional, Reversade, Bruno, additional, Gecz, Jozef, additional, Gilissen, Christian, additional, Brunner, Han G., additional, Kini, Usha, additional, Roepman, Ronald, additional, Nordgren, Ann, additional, and Kleefstra, Tjitske, additional
- Published
- 2016
- Full Text
- View/download PDF
11. THOC2 Mutations Implicate mRNA-Export Pathway in X-Linked Intellectual Disability
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Kumar, Raman, primary, Corbett, Mark A., additional, van Bon, Bregje W.M., additional, Woenig, Joshua A., additional, Weir, Lloyd, additional, Douglas, Evelyn, additional, Friend, Kathryn L., additional, Gardner, Alison, additional, Shaw, Marie, additional, Jolly, Lachlan A., additional, Tan, Chuan, additional, Hunter, Matthew F., additional, Hackett, Anna, additional, Field, Michael, additional, Palmer, Elizabeth E., additional, Leffler, Melanie, additional, Rogers, Carolyn, additional, Boyle, Jackie, additional, Bienek, Melanie, additional, Jensen, Corinna, additional, Van Buggenhout, Griet, additional, Van Esch, Hilde, additional, Hoffmann, Katrin, additional, Raynaud, Martine, additional, Zhao, Huiying, additional, Reed, Robin, additional, Hu, Hao, additional, Haas, Stefan A., additional, Haan, Eric, additional, Kalscheuer, Vera M., additional, and Gecz, Jozef, additional
- Published
- 2015
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12. Mutations in USP9X Are Associated with X-Linked Intellectual Disability and Disrupt Neuronal Cell Migration and Growth
- Author
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Homan, Claire C., primary, Kumar, Raman, additional, Nguyen, Lam Son, additional, Haan, Eric, additional, Raymond, F. Lucy, additional, Abidi, Fatima, additional, Raynaud, Martine, additional, Schwartz, Charles E., additional, Wood, Stephen A., additional, Gecz, Jozef, additional, and Jolly, Lachlan A., additional
- Published
- 2014
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13. A Noncoding, Regulatory Mutation Implicates HCFC1 in Nonsyndromic Intellectual Disability
- Author
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Huang, Lingli, primary, Jolly, Lachlan A., additional, Willis-Owen, Saffron, additional, Gardner, Alison, additional, Kumar, Raman, additional, Douglas, Evelyn, additional, Shoubridge, Cheryl, additional, Wieczorek, Dagmar, additional, Tzschach, Andreas, additional, Cohen, Monika, additional, Hackett, Anna, additional, Field, Michael, additional, Froyen, Guy, additional, Hu, Hao, additional, Haas, Stefan A., additional, Ropers, Hans-Hilger, additional, Kalscheuer, Vera M., additional, Corbett, Mark A., additional, and Gecz, Jozef, additional
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- 2012
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14. A Focal Epilepsy and Intellectual Disability Syndrome Is Due to a Mutation in TBC1D24
- Author
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Corbett, Mark A., primary, Bahlo, Melanie, additional, Jolly, Lachlan, additional, Afawi, Zaid, additional, Gardner, Alison E., additional, Oliver, Karen L., additional, Tan, Stanley, additional, Coffey, Amy, additional, Mulley, John C., additional, Dibbens, Leanne M., additional, Simri, Walid, additional, Shalata, Adel, additional, Kivity, Sara, additional, Jackson, Graeme D., additional, Berkovic, Samuel F., additional, and Gecz, Jozef, additional
- Published
- 2010
- Full Text
- View/download PDF
15. Mutations in USP9X Are Associated with X-Linked Intellectual Disability and Disrupt Neuronal Cell Migration and Growth
- Author
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Lachlan A. Jolly, F. Lucy Raymond, Eric Haan, Lam Son Nguyen, Raman Kumar, Claire C. Homan, Jozef Gecz, Fatima Abidi, Martine Raynaud, Charles E. Schwartz, Stephen A. Wood, Homan, Claire C, Kumar, Raman, Nguyen, Lam Son, Haan, Eric, Raymond, F Lucy, Abidi, Fatima, Raynaud, Martine, Schwartz, Charles E, Wood, Stephen A, Gecz, Jozef, and Jolly, Lachlan A
- Subjects
Male ,Proband ,Time Factors ,X-linked intellectual disability ,Neurogenesis ,Mutation, Missense ,USP9X ,Biology ,medicine.disease_cause ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Genes, X-Linked ,Report ,Intellectual Disability ,Genetics ,medicine ,Animals ,Humans ,Genetics(clinical) ,Gene ,Cytoskeleton ,Genetics (clinical) ,X chromosome ,Loss function ,Cell Proliferation ,030304 developmental biology ,Family Health ,Mice, Knockout ,Neurons ,Chromosomes, Human, X ,0303 health sciences ,Mutation ,disease-associated DNA variants ,Genetic Variation ,medicine.disease ,Phenotype ,DNA-Binding Proteins ,intellectual disability ,Knockout mouse ,Female ,Ubiquitin Thiolesterase ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
With a wealth of disease-associated DNA variants being recently reported, the challenges of providing their functional characterization are mounting. Previously, as part of a large systematic resequencing of the X chromosome in 208 unrelated families with nonsyndromic X-linked intellectual disability, we identified three unique variants (two missense and one protein truncating) in USP9X. To assess the functional significance of these variants, we took advantage of the Usp9x knockout mouse we generated. Loss of Usp9x causes reduction in both axonal growth and neuronal cell migration. Although overexpression of wild-type human USP9X rescued these defects, all three USP9X variants failed to rescue axonal growth, caused reduced USP9X protein localization in axonal growth cones, and (in 2/3 variants) failed to rescue neuronal cell migration. Interestingly, in one of these families, the proband was subsequently identified to have a microdeletion encompassing ARID1B, a known ID gene. Given our findings it is plausible that loss of function of both genes contributes to the individual's phenotype. This case highlights the complexity of the interpretations of genetic findings from genome-wide investigations. We also performed proteomics analysis of neurons from both the wild-type and Usp9x knockout embryos and identified disruption of the cytoskeleton as the main underlying consequence of the loss of Usp9x. Detailed clinical assessment of all three families with USP9X variants identified hypotonia and behavioral and morphological defects as common features in addition to ID. Together our data support involvement of all three USP9X variants in ID in these families and provide likely cellular and molecular mechanisms involved. Refereed/Peer-reviewed
- Published
- 2014
16. A Focal Epilepsy and Intellectual Disability Syndrome Is Due to a Mutation in TBC1D24
- Author
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Alison Gardner, Samuel F. Berkovic, Graeme D. Jackson, Leanne M. Dibbens, Melanie Bahlo, Walid Simri, Stanley Tan, Zaid Afawi, Lachlan A. Jolly, Jozef Gecz, Karen Oliver, Mark A. Corbett, Sara Kivity, Amy Coffey, John C. Mulley, Adel Shalata, Corbett, Mark A, Bahlo, Melanie, Jolly, Lachlan, Afawi, Zaid, Gardner, Alison E, Oliver, Karen L, Tan, Stanley, Coffey, Amy, Mulley, John C, Dibbens, Leanne M, Simri, Walid, Shalata, Adel, Kivity, Sara, Jackson, Graeme D, Berkovic, Samuel F, and Gecz, Jozef
- Subjects
focal epilepsy ,Male ,GTPase-activating protein ,Molecular Sequence Data ,Nerve Tissue Proteins ,Biology ,Mice ,Open Reading Frames ,Genetic linkage ,Intellectual Disability ,Report ,Intellectual disability ,medicine ,Genetics ,Animals ,Humans ,Gene family ,Genetics(clinical) ,gene mutation ,Amino Acid Sequence ,Phenotypic abnormality ,Cell Shape ,Gene ,Genetics (clinical) ,Neurons ,Massive parallel sequencing ,GTPase-Activating Proteins ,Chromosome Mapping ,Infant ,Membrane Proteins ,Syndrome ,medicine.disease ,Axons ,Pedigree ,Mutation ,Mutation (genetic algorithm) ,Female ,Epilepsies, Partial ,intellectual disability syndrome ,Carrier Proteins - Abstract
We characterized an autosomal-recessive syndrome of focal epilepsy, dysarthria, and mild to moderate intellectual disability in a consanguineous Arab-Israeli family associated with subtle cortical thickening. We used multipoint linkage analysis to map the causative mutation to a 3.2 Mb interval within 16p13.3 with a LOD score of 3.86. The linked interval contained 160 genes, many of which were considered to be plausible candidates to harbor the disease-causing mutation. To interrogate the interval in an efficient and unbiased manner, we used targeted sequence enrichment and massively parallel sequencing. By prioritizing unique variants that affected protein translation, a pathogenic mutation was identified in TBC1D24 (p.F251L), a gene of unknown function. It is a member of a large gene family encoding TBC domain proteins with predicted function as Rab GTPase activators. We show that TBC1D24 is expressed early in mouse brain and that TBC1D24 protein is a potent modulator of primary axonal arborization and specification in neuronal cells, consistent with the phenotypic abnormality described. Refereed/Peer-reviewed
- Published
- 2010
- Full Text
- View/download PDF
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