Search

Your search keyword '"Waddell, Leigh B."' showing total 49 results
Start Over Author "Waddell, Leigh B."
49 results on '"Waddell, Leigh B."'

1. Genome Sequencing for Diagnosing Rare Diseases

Author

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

Published
2024
Full Text
View/download PDF

2. Genome and RNA sequencing boost neuromuscular diagnoses to 62% from 34% with exome sequencing alone

Author

Marchant, Rhett G., primary, Bryen, Samantha J., additional, Bahlo, Melanie, additional, Cairns, Anita, additional, Chao, Katherine R., additional, Corbett, Alastair, additional, Davis, Mark R., additional, Ganesh, Vijay S., additional, Ghaoui, Roula, additional, Jones, Kristi J., additional, Kornberg, Andrew J., additional, Lek, Monkol, additional, Liang, Christina, additional, MacArthur, Daniel G., additional, Oates, Emily C., additional, O'Donnell‐Luria, Anne, additional, O'Grady, Gina L., additional, Osei‐Owusu, Ikeoluwa A., additional, Rafehi, Haloom, additional, Reddel, Stephen W., additional, Roxburgh, Richard H., additional, Ryan, Monique M., additional, Sandaradura, Sarah A., additional, Scott, Liam W., additional, Valkanas, Elise, additional, Weisburd, Ben, additional, Young, Helen, additional, Evesson, Frances J., additional, Waddell, Leigh B., additional, and Cooper, Sandra T., additional

Published
2024
Full Text
View/download PDF

4. Biallelic and monoallelic variants in PLXNA1 are implicated in a novel neurodevelopmental disorder with variable cerebral and eye anomalies

Author

Dworschak, Gabriel C., Punetha, Jaya, Kalanithy, Jeshurun C., Mingardo, Enrico, Erdem, Haktan B., Akdemir, Zeynep C., Karaca, Ender, Mitani, Tadahiro, Marafi, Dana, Fatih, Jawid M., Jhangiani, Shalini N., Hunter, Jill V., Dakal, Tikam Chand, Dhabhai, Bhanupriya, Dabbagh, Omar, Alsaif, Hessa S., Alkuraya, Fowzan S., Maroofian, Reza, Houlden, Henry, Efthymiou, Stephanie, Dominik, Natalia, Salpietro, Vincenzo, Sultan, Tipu, Haider, Shahzad, Bibi, Farah, Thiele, Holger, Hoefele, Julia, Riedhammer, Korbinian M., Wagner, Matias, Guella, Ilaria, Demos, Michelle, Keren, Boris, Buratti, Julien, Charles, Perrine, Nava, Caroline, Héron, Delphine, Heide, Solveig, Valkanas, Elise, Waddell, Leigh B., Jones, Kristi J., Oates, Emily C., Cooper, Sandra T., MacArthur, Daniel, Syrbe, Steffen, Ziegler, Andreas, Platzer, Konrad, Okur, Volkan, Chung, Wendy K., O’Shea, Sarah A., Alcalay, Roy, Fahn, Stanley, Mark, Paul R., Guerrini, Renzo, Vetro, Annalisa, Hudson, Beth, Schnur, Rhonda E., Hoganson, George E., Burton, Jennifer E., McEntagart, Meriel, Lindenberg, Tobias, Yilmaz, Öznur, Odermatt, Benjamin, Pehlivan, Davut, Posey, Jennifer E., Lupski, James R., and Reutter, Heiko

Published
2021
Full Text
View/download PDF

7. Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

Author

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

Published
2023
Full Text
View/download PDF

9. Connective tissue presentation in two families expands the phenotypic spectrum of PYROXD1 disorders

Author

Evesson, Frances J, primary, Dziaduch, Gregory, additional, Bryen, Samantha J, additional, Moore, Francesca, additional, Pittman, Sara, additional, Devanapalli, Beena, additional, Waddell, Leigh B, additional, Ryan, Monique M, additional, Menezes, Manoj P, additional, Weihl, Conrad C, additional, Tolun, Adviye Ayper, additional, Zaidman, Craig, additional, Young, Helen, additional, Adès, Lesley C, additional, and Cooper, Sandra T, additional

Published
2023
Full Text
View/download PDF

10. Compound heterozygous splicing variants expand the genotypic spectrum of EMC1‐related disorders

Author

Bryen, Samantha J., primary, Zhang, Katharine, additional, Dziaduch, Gregory, additional, Bommireddipalli, Shobhana, additional, Naseri, Take, additional, Reupena, Muagututi'a Sefuiva, additional, Viali, Satupa'itea, additional, Minster, Ryan L., additional, Waddell, Leigh B., additional, Charlton, Amanda, additional, O'Grady, Gina L., additional, Evesson, Frances J., additional, and Cooper, Sandra T., additional

Published
2023
Full Text
View/download PDF

12. Prevalence, parameters, and pathogenic mechanisms for splice-altering acceptor variants that disrupt the AG exclusion zone

Author

Bryen, Samantha J., primary, Yuen, Michaela, additional, Joshi, Himanshu, additional, Dawes, Ruebena, additional, Zhang, Katharine, additional, Lu, Jessica K., additional, Jones, Kristi J., additional, Liang, Christina, additional, Wong, Wui-Kwan, additional, Peduto, Anthony J., additional, Waddell, Leigh B., additional, Evesson, Frances J., additional, and Cooper, Sandra T., additional

Published
2022
Full Text
View/download PDF

13. Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant

Author

Sandaradura, Sarah A., Bournazos, Adam, Mallawaarachchi, Amali, Cummings, Beryl B., Waddell, Leigh B., Jones, Kristi J., Troedson, Christopher, Sudarsanam, Annapurna, Nash, Benjamin M., Peters, Gregory B., Algar, Elizabeth M., MacArthur, Daniel G., North, Kathryn N., Brammah, Susan, Charlton, Amanda, Laing, Nigel G., Wilson, Meredith J., Davis, Mark R., and Cooper, Sandra T.

Published
2018
Full Text
View/download PDF

16. Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies

Author

Ilkovski, Biljana, Pagnamenta, Alistair T., OʼGrady, Gina L., Kinoshita, Taroh, Howard, Malcolm F., Lek, Monkol, Thomas, Brett, Turner, Anne, Christodoulou, John, Sillence, David, Knight, Samantha J.L., Popitsch, Niko, Keays, David A., Anzilotti, Consuelo, Goriely, Anne, Waddell, Leigh B., Brilot, Fabienne, North, Kathryn N., Kanzawa, Noriyuki, Macarthur, Daniel G., Taylor, Jenny C., Kini, Usha, Murakami, Yoshiko, and Clarke, Nigel F.

Published
2015
Full Text
View/download PDF

17. Expanding the phenotype of GMPPB mutations

Author

Cabrera-Serrano, Macarena, Ghaoui, Roula, Ravenscroft, Gianina, Johnsen, Russell D., Davis, Mark R., Corbett, Alastair, Reddel, Stephen, Sue, Carolyn M., Liang, Christina, Waddell, Leigh B., Kaur, Simranpreet, Lek, Monkol, North, Kathryn N., MacArthur, Daniel G., Lamont, Phillipa J., Clarke, Nigel F., and Laing, Nigel G.

Published
2015
Full Text
View/download PDF

18. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy

Author

Yuen, Michaela, Sandaradura, Sarah A., Dowling, James J., Kostyukova, Alla S., Moroz, Natalia, Quinlan, Kate G., Lehtokari, Vilma-Lotta, Ravenscroft, Gianina, Todd, Emily J., Ceyhan-Birsoy, Ozge, Gokhin, David S., Maluenda, Jérome, Lek, Monkol, Nolent, Flora, Pappas, Christopher T., Novak, Stefanie M., DʼAmico, Adele, Malfatti, Edoardo, Thomas, Brett P., Gabriel, Stacey B., Gupta, Namrata, Daly, Mark J., Ilkovski, Biljana, Houweling, Peter J., Davidson, Ann E., Swanson, Lindsay C., Brownstein, Catherine A., Gupta, Vandana A., Medne, Livija, Shannon, Patrick, Martin, Nicole, Bick, David P., Flisberg, Anders, Holmberg, Eva, Van den Bergh, Peter, Lapunzina, Pablo, Waddell, Leigh B., Sloboda, Darcée D., Bertini, Enrico, Chitayat, David, Telfer, William R., Laquerrière, Annie, Gregorio, Carol C., Ottenheijm, Coen A.C., Bönnemann, Carsten G., Pelin, Katarina, Beggs, Alan H., Hayashi, Yukiko K., Romero, Norma B., Laing, Nigel G., Nishino, Ichizo, Wallgren-Pettersson, Carina, Melki, Judith, Fowler, Velia M., MacArthur, Daniel G., North, Kathryn N., and Clarke, Nigel F.

Published
2014
Full Text
View/download PDF

19. WGS and RNA Studies Diagnose Noncoding DMD Variants in Males With High Creatine Kinase

Author

Waddell, Leigh B., primary, Bryen, Samantha J., additional, Cummings, Beryl B., additional, Bournazos, Adam, additional, Evesson, Frances J., additional, Joshi, Himanshu, additional, Marshall, Jamie L., additional, Tukiainen, Taru, additional, Valkanas, Elise, additional, Weisburd, Ben, additional, Sadedin, Simon, additional, Davis, Mark R., additional, Faiz, Fathimath, additional, Gooding, Rebecca, additional, Sandaradura, Sarah A., additional, O'Grady, Gina L., additional, Tchan, Michel C., additional, Mowat, David R., additional, Oates, Emily C., additional, Farrar, Michelle A., additional, Sampaio, Hugo, additional, Ma, Alan, additional, Neas, Katherine, additional, Wang, Min-Xia, additional, Charlton, Amanda, additional, Chan, Charles, additional, Kenwright, Diane N., additional, Graf, Nicole, additional, Arbuckle, Susan, additional, Clarke, Nigel F., additional, MacArthur, Daniel G., additional, Jones, Kristi J., additional, Lek, Monkol, additional, and Cooper, Sandra T., additional

Published
2021
Full Text
View/download PDF

20. Mutations in cardiac T-Box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

Author

Kirk, Edwin P., Sunde, Margaret, Costa Mauro W., Rankin, Scott A., Wolstein Orit, Castro, M. Leticia, Butler, Tanya L., Changbaig, Hyun, Guo, Gunglan, Otway, Robyn, Mackay, Jeol P., Waddell, Leigh B., Cole, Andrew D., Hayward, Christopher, Keogh, Anne, Macdonald, Peter, Griffiths, Lyn, Fatkin, Diane, Sholler, Gary F., Zorn, Aaron M., Fenely, Michael P., Winlaw, David S., and Harvey, Richard P.

Subjects
Gene mutations -- Research, Genetic transcription -- Research, Genetic research, Biological sciences
Abstract

The article describes the T-box family transcription factor gene TBX20 that acts in a conserved regulatory network, guiding heart formation and patterning in diverse species.

Published
2007

25. Pathogenic deep intronic MTM1 variant activates a pseudo-exon encoding a nonsense codon resulting in severe X-linked myotubular myopathy

Author

Bryen, Samantha J., primary, Oates, Emily C., additional, Evesson, Frances J., additional, Lu, Jessica K., additional, Waddell, Leigh B., additional, Joshi, Himanshu, additional, Ryan, Monique M., additional, Cummings, Beryl B., additional, McLean, Catriona A., additional, MacArthur, Daniel G., additional, Kornberg, Andrew J., additional, and Cooper, Sandra T., additional

Published
2020
Full Text
View/download PDF

26. Importance of muscle biopsy to establish pathogenicity of DMD missense and splice variants

Author

Jones, Hannah F, primary, Bryen, Samantha J, additional, Waddell, Leigh B, additional, Bournazos, Adam, additional, Davis, Mark, additional, Farrar, Michelle A, additional, McLean, Catriona A, additional, Mowat, David R, additional, Sampaio, Hugo, additional, Woodcock, Ian R, additional, Ryan, Monique M, additional, Jones, Kristi J, additional, and Cooper, Sandra T, additional

Published
2019
Full Text
View/download PDF

28. Congenital Titinopathy: Comprehensive characterization and pathogenic insights

Author

Oates, Emily C., Jones, Kristi J., Donkervoort, Sandra, Charlton, Amanda, Brammah, Susan, Smith, John E., Ware, James S., Yau, Kyle S., Swanson, Lindsay C., Whiffin, Nicola, Peduto, Anthony J., Bournazos, Adam, Waddell, Leigh B., Farrar, Michelle A., Sampaio, Hugo A., Teoh, Hooi Ling, Lamont, Phillipa J., Mowat, David, Fitzsimons, Robin B., Corbett, Alastair J., Ryan, Monique M., O'Grady, Gina L., Sandaradura, Sarah A., Ghaoui, Roula, Joshi, Himanshu, Marshall, Jamie L., Nolan, Melinda A., Kaur, Simranpreet, Punetha, Jaya, Töpf, Ana, Harris, Elizabeth, Bakshi, Madhura, Genetti, Casie A., Marttila, Minttu, Werlauff, Ulla, Streichenberger, Nathalie, Pestronk, Alan, Mazanti, Ingrid, Pinner, Jason R., Vuillerot, Carole, Grosmann, Carla, Camacho, Ana, Mohassel, Payam, Leach, Meganne E., Foley, A. Reghan, Bharucha-Goebel, Diana, Collins, James, Connolly, Anne M., Gilbreath, Heather R., Iannaccone, Susan T., Castro, Diana, Cummings, Beryl B., Webster, Richard I., Lazaro, Leïla, Vissing, John, Coppens, Sandra, Deconinck, Nicolas, Luk, Ho Ming, Thomas, Neil H., Foulds, Nicola C., Illingworth, Marjorie A., Ellard, Sian, McLean, Catriona A., Phadke, Rahul, Ravenscroft, Gianina, Witting, Nanna, Hackman, Peter, Richard, Isabelle, Cooper, Sandra T., Kamsteeg, Erik Jan, Hoffman, Eric P., Bushby, Kate, Straub, Volker, Udd, Bjarne, Ferreiro, Ana, North, Kathryn N., Clarke, Nigel F., Lek, Monkol, Beggs, Alan H., Bönnemann, Carsten G., MacArthur, Daniel G., Granzier, Henk, Davis, Mark R., and Laing, Nigel G.

Subjects
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
Abstract

Contains fulltext : 196367.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder. METHODS: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients. RESULTS: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder. INTERPRETATION: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124.

Published
2018

30. Pathogenic deep intronic MTM1variant activates a pseudo-exon encoding a nonsense codon resulting in severe X-linked myotubular myopathy

Author

Bryen, Samantha J., Oates, Emily C., Evesson, Frances J., Lu, Jessica K., Waddell, Leigh B., Joshi, Himanshu, Ryan, Monique M., Cummings, Beryl B., McLean, Catriona A., MacArthur, Daniel G., Kornberg, Andrew J., and Cooper, Sandra T.

Abstract

X-linked myotubular myopathy (XLMTM) is a severe congenital myopathy characterised by generalised weakness and respiratory insufficiency. XLMTM is associated with pathogenic variants in MTM1; a gene encoding the lipid phosphatase myotubularin. Whole genome sequencing (WGS) of an exome-negative male proband with severe hypotonia, respiratory insufficiency and centralised nuclei on muscle biopsy identified a deep intronic MTM1variant NG_008199.1(NM_000252.2):c.1468-577A>G, which strengthened a cryptic 5' splice site (A>G substitution at the +5 position). Muscle RNA sequencing was non-diagnostic due to low read depth. Reverse transcription PCR (RT-PCR) of muscle RNA confirmed the c.1468-577A>G variant activates inclusion of a pseudo-exon encoding a premature stop codon into all detected MTM1transcripts. Western blot analysis establishes deficiency of myotubularin protein, consistent with the severe XLMTM phenotype. We expand the genotypic spectrum of XLMTM and highlight benefits of screening non-coding regions of MTM1in male probands with phenotypically concordant XLMTM who remain undiagnosed following exome sequencing.

Published
2021
Full Text
View/download PDF

31. Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization

Author

O’Grady, Gina L., primary, Best, Heather A., additional, Sztal, Tamar E., additional, Schartner, Vanessa, additional, Sanjuan-Vazquez, Myriam, additional, Donkervoort, Sandra, additional, Abath Neto, Osorio, additional, Sutton, Roger Bryan, additional, Ilkovski, Biljana, additional, Romero, Norma Beatriz, additional, Stojkovic, Tanya, additional, Dastgir, Jahannaz, additional, Waddell, Leigh B., additional, Boland, Anne, additional, Hu, Ying, additional, Williams, Caitlin, additional, Ruparelia, Avnika A., additional, Maisonobe, Thierry, additional, Peduto, Anthony J., additional, Reddel, Stephen W., additional, Lek, Monkol, additional, Tukiainen, Taru, additional, Cummings, Beryl B., additional, Joshi, Himanshu, additional, Nectoux, Juliette, additional, Brammah, Susan, additional, Deleuze, Jean-François, additional, Ing, Viola Oorschot, additional, Ramm, Georg, additional, Ardicli, Didem, additional, Nowak, Kristen J., additional, Talim, Beril, additional, Topaloglu, Haluk, additional, Laing, Nigel G., additional, North, Kathryn N., additional, MacArthur, Daniel G., additional, Friant, Sylvie, additional, Clarke, Nigel F., additional, Bryson-Richardson, Robert J., additional, Bönnemann, Carsten G., additional, Laporte, Jocelyn, additional, and Cooper, Sandra T., additional

Published
2016
Full Text
View/download PDF

32. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy: corrigendum

Author

Yuen, Michaela, Sandaradura, Sarah A, Dowling, James J, Kostyukova, Alla S, Moroz, Natalia, Quinlan, Kate G, Lehtokari, Vilma-Lotta, Ravenscroft, Gianina, Todd, Emily J, Ceyhan-Birsoy, Ozge, Gokhin, David S, Maluenda, Jérome, Lek, Monkol, Nolent, Flora, Pappas, Christopher T, Novak, Stefanie M, D'Amico, Adele, Malfatti, Edoardo, Thomas, Brett P, Gabriel, Stacey B, Gupta, Namrata, Daly, Mark J, Ilkovski, Biljana, Houweling, Peter J, Davidson, Ann E, Swanson, Lindsay C, Brownstein, Catherine A, Gupta, Vandana A, Medne, Livija, Shannon, Patrick, Martin, Nicole, Bick, David P, Flisberg, Anders, Holmberg, Eva, Van den Bergh, Peter, Lapunzina, Pablo, Waddell, Leigh B, Sloboda, Darcée D, Bertini, Enrico, Chitayat, David, Telfer, William R, Laquerrière, Annie, Gregorio, Carol C, Ottenheijm, Coen A C, Bönnemann, Carsten G, Pelin, Katarina, Beggs, Alan H, Hayashi, Yukiko K, Romero, Norma B, Laing, Nigel G, Nishino, Ichizo, Wallgren-Pettersson, Carina, Melki, Judith, Fowler, Velia M, MacArthur, Daniel G, North, Kathryn N, Clarke, Nigel F, Clinical chemistry, Physiology, and ICaR - Heartfailure and pulmonary arterial hypertension

Published
2015

35. Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases

Author

Punetha, Jaya, primary, Kesari, Akanchha, additional, Uapinyoying, Prech, additional, Giri, Mamta, additional, Clarke, Nigel F., additional, Waddell, Leigh B., additional, North, Kathryn N., additional, Ghaoui, Roula, additional, O’Grady, Gina L., additional, Oates, Emily C., additional, Sandaradura, Sarah A., additional, Bönnemann, Carsten G., additional, Donkervoort, Sandra, additional, Plotz, Paul H., additional, Smith, Edward C., additional, Tesi-Rocha, Carolina, additional, Bertorini, Tulio E., additional, Tarnopolsky, Mark A., additional, Reitter, Bernd, additional, Hausmanowa-Petrusewicz, Irena, additional, and Hoffman, Eric P., additional

Published
2016
Full Text
View/download PDF

36. Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive <italic>TNNT3</italic> splice variant.

Author

Sandaradura, Sarah A., Bournazos, Adam, Mallawaarachchi, Amali, Cummings, Beryl B., Waddell, Leigh B., Jones, Kristi J., Troedson, Christopher, Sudarsanam, Annapurna, Nash, Benjamin M., Peters, Gregory B., Algar, Elizabeth M., MacArthur, Daniel G., North, Kathryn N., Brammah, Susan, Charlton, Amanda, Laing, Nigel G., Wilson, Meredith J., Davis, Mark R., and Cooper, Sandra T.

Abstract

Abstract: A male neonate presented with severe weakness, hypotonia, contractures and congenital scoliosis. Skeletal muscle specimens showed marked atrophy and degeneration of fast fibers with striking nemaline rods and hypertrophy of slow fibers that were ultrastructurally normal. A neuromuscular gene panel identified a homozygous essential splice variant in TNNT3 (chr11:1956150G > A, NM_006757.3:c.681+1G > A). TNNT3 encodes skeletal troponin‐Tfast and is associated with autosomal dominant distal arthrogryposis. TNNT3 has not previously been associated with nemaline myopathy (NM), a rare congenital myopathy linked to defects in proteins associated with thin filament structure and regulation. cDNA studies confirmed pathogenic consequences of the splice variant, eliciting exon‐skipping and intron retention events leading to a frameshift. Western blot showed deficiency of troponin‐Tfast protein with secondary loss of troponin‐Ifast. We establish a homozygous splice variant in TNNT3 as the likely cause of severe congenital NM with distal arthrogryposis, characterized by specific involvement of Type‐2 fibers and deficiency of troponin‐Tfast. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

39. Mutations inPIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies

Author

Ilkovski, Biljana, primary, Pagnamenta, Alistair T., additional, O'Grady, Gina L., additional, Kinoshita, Taroh, additional, Howard, Malcolm F., additional, Lek, Monkol, additional, Thomas, Brett, additional, Turner, Anne, additional, Christodoulou, John, additional, Sillence, David, additional, Knight, Samantha J.L., additional, Popitsch, Niko, additional, Keays, David A., additional, Anzilotti, Consuelo, additional, Goriely, Anne, additional, Waddell, Leigh B., additional, Brilot, Fabienne, additional, North, Kathryn N., additional, Kanzawa, Noriyuki, additional, Macarthur, Daniel G., additional, Taylor, Jenny C., additional, Kini, Usha, additional, Murakami, Yoshiko, additional, and Clarke, Nigel F., additional

Published
2015
Full Text
View/download PDF

40. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.

Author

Cummings, Beryl B., Marshall, Jamie L., Tukiainen, Taru, Lek, Monkol, Donkervoort, Sandra, Foley, A. Reghan, Bolduc, Veronique, Waddell, Leigh B., Sandaradura, Sarah A., O'Grady, Gina L., Estrella, Elicia, Reddy, Hemakumar M., Zhao, Fengmei, Weisburd, Ben, Karczewski, Konrad J., O'Donnell-Luria, Anne H., Birnbaum, Daniel, Sarkozy, Anna, Ying Hu, and Gonorazky, Hernan

Subjects
HUMAN chromosome abnormality diagnosis, MENDEL'S law, RNA sequencing, RARE diseases, DIAGNOSIS
Abstract

The article discusses the improvement of genetic diagnosis in Mendelian disease with transcriptome sequencing. It cites on the rates for genomic analyses in rare diseases in which transcriptome sequencing is used as a diagnostic tool patients with genetically undiagnosed rare muscle disorders. The article also discusses the study that represents large systematic application of transcriptome sequencing to rare disease diagnosis.

Published
2017
Full Text
View/download PDF

42. Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations

Author

Tajsharghi, Homa, primary, Hammans, Simon, additional, Lindberg, Christopher, additional, Lossos, Alexander, additional, Clarke, Nigel F, additional, Mazanti, Ingrid, additional, Waddell, Leigh B, additional, Fellig, Yakov, additional, Foulds, Nicola, additional, Katifi, Haider, additional, Webster, Richard, additional, Raheem, Olayinka, additional, Udd, Bjarne, additional, Argov, Zohar, additional, and Oldfors, Anders, additional

Published
2013
Full Text
View/download PDF

43. Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and Limb-Girdle Muscular Dystrophies Associated with Hypoglycosylation of α-Dystroglycan

Author

Carss, Keren J., primary, Stevens, Elizabeth, additional, Foley, A. Reghan, additional, Cirak, Sebahattin, additional, Riemersma, Moniek, additional, Torelli, Silvia, additional, Hoischen, Alexander, additional, Willer, Tobias, additional, van Scherpenzeel, Monique, additional, Moore, Steven A., additional, Messina, Sonia, additional, Bertini, Enrico, additional, Bönnemann, Carsten G., additional, Abdenur, Jose E., additional, Grosmann, Carla M., additional, Kesari, Akanchha, additional, Punetha, Jaya, additional, Quinlivan, Ros, additional, Waddell, Leigh B., additional, Young, Helen K., additional, Wraige, Elizabeth, additional, Yau, Shu, additional, Brodd, Lina, additional, Feng, Lucy, additional, Sewry, Caroline, additional, MacArthur, Daniel G., additional, North, Kathryn N., additional, Hoffman, Eric, additional, Stemple, Derek L., additional, Hurles, Matthew E., additional, van Bokhoven, Hans, additional, Campbell, Kevin P., additional, Lefeber, Dirk J., additional, Lin, Yung-Yao, additional, and Muntoni, Francesco, additional

Published
2013
Full Text
View/download PDF

44. Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations.

Author

Tajsharghi, Homa, Hammans, Simon, Lindberg, Christopher, Lossos, Alexander, Clarke, Nigel F, Mazanti, Ingrid, Waddell, Leigh B, Fellig, Yakov, Foulds, Nicola, Katifi, Haider, Webster, Richard, Raheem, Olayinka, Udd, Bjarne, Argov, Zohar, and Oldfors, Anders

Subjects
MYOSIN, MUSCLE diseases, GENETIC disorders, HEREDITY, GENETIC mutation
Abstract

Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

45. Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis.

Author

Wojcik MH, Lemire G, Zaki MS, Wissman M, Win W, White S, Weisburd B, Waddell LB, Verboon JM, VanNoy GE, Töpf A, Tan TY, Straub V, Stenton SL, Snow H, Singer-Berk M, Silver J, Shril S, Seaby EG, Schneider R, Sankaran VG, Sanchis-Juan A, Russell KA, Reinson K, Ravenscroft G, Pierce EA, Place EM, Pajusalu S, Pais L, Õunap K, Osei-Owusu I, Okur V, Oja KT, O'Leary M, O'Heir E, Morel C, Marchant RG, Mangilog BE, Madden JA, MacArthur D, Lovgren A, Lerner-Ellis JP, Lin J, Laing N, Hildebrandt F, Groopman E, Goodrich J, Gleeson JG, Ghaoui R, Genetti CA, Gazda HT, Ganesh VS, Ganapathy M, Gallacher L, Fu J, Evangelista E, England E, Donkervoort S, DiTroia S, Cooper ST, Chung WK, Christodoulou J, Chao KR, Cato LD, Bujakowska KM, Bryen SJ, Brand H, Bonnemann C, Beggs AH, Baxter SM, Agrawal PB, Talkowski M, Austin-Tse C, Rehm HL, and O'Donnell-Luria A

Abstract

Background: Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages of GS within a phenotypically diverse cohort., Methods: GS was performed for 744 individuals with rare disease who were genetically undiagnosed. Analysis included review of single nucleotide, indel, structural, and mitochondrial variants., Results: We successfully solved 218/744 (29.3%) cases using GS, with most solves involving established disease genes (157/218, 72.0%). Of all solved cases, 148 (67.9%) had previously had non-diagnostic ES. We systematically evaluated the 218 causal variants for features requiring GS to identify and 61/218 (28.0%) met these criteria, representing 8.2% of the entire cohort. These included small structural variants (13), copy neutral inversions and complex rearrangements (8), tandem repeat expansions (6), deep intronic variants (15), and coding variants that may be more easily found using GS related to uniformity of coverage (19)., Conclusion: We describe the diagnostic yield of GS in a large and diverse cohort, illustrating several types of pathogenic variation eluding ES or other techniques. Our results reveal a higher diagnostic yield of GS, supporting the utility of a genome-first approach, with consideration of GS as a secondary or tertiary test when higher-resolution structural variant analysis is needed or there is a strong clinical suspicion for a condition and prior targeted genetic testing has been negative.

Published
2023
Full Text
View/download PDF

46. Congenital Titinopathy: Comprehensive characterization and pathogenic insights.

Author

Oates EC, Jones KJ, Donkervoort S, Charlton A, Brammah S, Smith JE 3rd, Ware JS, Yau KS, Swanson LC, Whiffin N, Peduto AJ, Bournazos A, Waddell LB, Farrar MA, Sampaio HA, Teoh HL, Lamont PJ, Mowat D, Fitzsimons RB, Corbett AJ, Ryan MM, O'Grady GL, Sandaradura SA, Ghaoui R, Joshi H, Marshall JL, Nolan MA, Kaur S, Punetha J, Töpf A, Harris E, Bakshi M, Genetti CA, Marttila M, Werlauff U, Streichenberger N, Pestronk A, Mazanti I, Pinner JR, Vuillerot C, Grosmann C, Camacho A, Mohassel P, Leach ME, Foley AR, Bharucha-Goebel D, Collins J, Connolly AM, Gilbreath HR, Iannaccone ST, Castro D, Cummings BB, Webster RI, Lazaro L, Vissing J, Coppens S, Deconinck N, Luk HM, Thomas NH, Foulds NC, Illingworth MA, Ellard S, McLean CA, Phadke R, Ravenscroft G, Witting N, Hackman P, Richard I, Cooper ST, Kamsteeg EJ, Hoffman EP, Bushby K, Straub V, Udd B, Ferreiro A, North KN, Clarke NF, Lek M, Beggs AH, Bönnemann CG, MacArthur DG, Granzier H, Davis MR, and Laing NG

Subjects
Female, Humans, Male, Mutation genetics, Phenotype, Protein Isoforms genetics, Cardiomyopathy, Dilated congenital, Connectin genetics, Muscle Proteins genetics, Muscle, Skeletal pathology
Abstract

Objective: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder., Methods: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients., Results: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder., Interpretation: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124., (© 2018 American Neurological Association.)

Published
2018
Full Text
View/download PDF

47. Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization.

Author

O'Grady GL, Best HA, Sztal TE, Schartner V, Sanjuan-Vazquez M, Donkervoort S, Abath Neto O, Sutton RB, Ilkovski B, Romero NB, Stojkovic T, Dastgir J, Waddell LB, Boland A, Hu Y, Williams C, Ruparelia AA, Maisonobe T, Peduto AJ, Reddel SW, Lek M, Tukiainen T, Cummings BB, Joshi H, Nectoux J, Brammah S, Deleuze JF, Ing VO, Ramm G, Ardicli D, Nowak KJ, Talim B, Topaloglu H, Laing NG, North KN, MacArthur DG, Friant S, Clarke NF, Bryson-Richardson RJ, Bönnemann CG, Laporte J, and Cooper ST

Subjects
Amino Acid Sequence, Animals, COS Cells, Cell Nucleus metabolism, Chlorocebus aethiops, Cohort Studies, Creatine Kinase genetics, Creatine Kinase metabolism, Cytoplasm metabolism, Distal Myopathies pathology, ELAV-Like Protein 4 genetics, ELAV-Like Protein 4 metabolism, Female, Flavoproteins metabolism, Gene Deletion, Genome-Wide Association Study, Glutathione Reductase genetics, Glutathione Reductase metabolism, HEK293 Cells, Humans, Male, Muscle, Skeletal pathology, Mutation, Missense, Myopathies, Structural, Congenital pathology, Oxidoreductases metabolism, Pedigree, Protein Conformation, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Zebrafish genetics, Cell Nucleus genetics, Distal Myopathies genetics, Genetic Variation, Myopathies, Structural, Congenital genetics, Oxidoreductases genetics
Abstract

This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalized nuclei, myofibrillar disorganization, desmin-positive inclusions, and thickened Z-bands. PYROXD1 is a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins (FAD-binding) and catalyze pyridine-nucleotide-dependent (NAD/NADH) reduction of thiol residues in other proteins. Complementation experiments in yeast lacking glutathione reductase glr1 show that human PYROXD1 has reductase activity that is strongly impaired by the disease-associated missense mutations. Immunolocalization studies in human muscle and zebrafish myofibers demonstrate that PYROXD1 localizes to the nucleus and to striated sarcomeric compartments. Zebrafish with ryroxD1 knock-down recapitulate features of PYROXD1 myopathy with sarcomeric disorganization, myofibrillar aggregates, and marked swimming defect. We characterize variants in the oxidoreductase PYROXD1 as a cause of early-onset myopathy with distinctive histopathology and introduce altered redox regulation as a primary cause of congenital muscle disease., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2016
Full Text
View/download PDF

48. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy.

Author

Yuen M, Sandaradura SA, Dowling JJ, Kostyukova AS, Moroz N, Quinlan KG, Lehtokari VL, Ravenscroft G, Todd EJ, Ceyhan-Birsoy O, Gokhin DS, Maluenda J, Lek M, Nolent F, Pappas CT, Novak SM, D'Amico A, Malfatti E, Thomas BP, Gabriel SB, Gupta N, Daly MJ, Ilkovski B, Houweling PJ, Davidson AE, Swanson LC, Brownstein CA, Gupta VA, Medne L, Shannon P, Martin N, Bick DP, Flisberg A, Holmberg E, Van den Bergh P, Lapunzina P, Waddell LB, Sloboda DD, Bertini E, Chitayat D, Telfer WR, Laquerrière A, Gregorio CC, Ottenheijm CA, Bönnemann CG, Pelin K, Beggs AH, Hayashi YK, Romero NB, Laing NG, Nishino I, Wallgren-Pettersson C, Melki J, Fowler VM, MacArthur DG, North KN, and Clarke NF

Published
2015
Full Text
View/download PDF

49. GATA4 mutations in 357 unrelated patients with congenital heart malformation.

Author

Butler TL, Esposito G, Blue GM, Cole AD, Costa MW, Waddell LB, Walizada G, Sholler GF, Kirk EP, Feneley M, Harvey RP, and Winlaw DS

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Cohort Studies, GATA4 Transcription Factor metabolism, Homeobox Protein Nkx-2.5, Homeodomain Proteins metabolism, Humans, Infant, Infant, Newborn, Middle Aged, Mutation, T-Box Domain Proteins metabolism, Transcription Factors metabolism, Transcriptional Activation genetics, Young Adult, GATA4 Transcription Factor genetics, Heart Defects, Congenital genetics, Zinc Fingers genetics
Abstract

Congenital heart disease (CHD) represents one of the most common birth defects, but the genetic causes remain largely unknown. Mutations in GATA4, encoding a zinc finger transcription factor with a pivotal role in heart development, have been associated with CHD in several familial cases and a small subset of sporadic patients. To estimate the pathogenetic role of GATA4 in CHD, we screened for mutations in 357 unrelated patients with different congenital heart malformations. In addition to nine synonymous changes, we identified two known (A411V and D425N) and two novel putative mutations (G69D and P163R) in five patients with atrial or ventricular septal defects that were not seen in control subjects. The four mutations did not show altered GATA4 transcriptional activity in synergy with the transcription factors NKX2-5 and TBX20. Our data expand the spectrum of mutations associated with cardiac septal defects but do not support GATA4 mutations as a common cause of CHD.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results