33 results on '"Mackay DJG"'
Search Results
2. Growth hormone improves short-term growth in patients with temple syndrome
- Author
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Oluwakemi Lokulo-Sodipe, Diana S Brightman, Mackay Djg, Searle B, I.K. Temple, Andrew Dauber, and Justin H Davies
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Medicine ,In patient ,Temple Syndrome ,Short term growth ,Growth hormone ,business - Published
- 2019
- Full Text
- View/download PDF
3. Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement
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Christian P. Kratz, Le Bouc Y, Ibrahim A, Jennifer M. Kalish, Tatton-Brown, Frédéric Brioude, Sylvie Rossignol, Jair Tenorio, Kilby, Giovanni Battista Ferrero, Irène Netchine, De Pellegrin M, Raoul C.M. Hennekam, Silvia Russo, Fiona Macdonald, Trevor Cole, Eamonn R. Maher, Mackay Djg, Karen Grønskov, Edmund J. Ladusans, Khalid Hussain, Licia Peruzzi, Saskia M. Maas, Andrea Riccio, Susanne E Boonen, Monica Bertoletti, Pablo Lapunzina, Zeynep Tümer, oze C, Jet Bliek, Alison Foster, Chiara Tortora, Thomas Eggermann, Guido Cocchi, Caroleen Shipster, Małgorzata Krajewska-Walasek, Dirk Prawitt, Robert Baker, Katrin Õunap, Alessandro Mussa, Agata Skórka, Human Genetics, Paediatric Genetics, APH - Quality of Care, ARD - Amsterdam Reproduction and Development, Maher, Eamonn [0000-0002-6226-6918], and Apollo - University of Cambridge Repository
- Subjects
medicine.medical_specialty ,Beckwith-Wiedemann Syndrome ,Consensus ,DNA Copy Number Variations ,Reproductive Techniques, Assisted ,Statement (logic) ,Beckwith–Wiedemann syndrome ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,0302 clinical medicine ,Prenatal Diagnosis ,Humans ,Medicine ,030304 developmental biology ,0303 health sciences ,business.industry ,Expert consensus ,DNA Methylation ,Neoplasms, Germ Cell and Embryonal ,medicine.disease ,3. Good health ,Molecular Diagnostic Techniques ,030220 oncology & carcinogenesis ,Family medicine ,business - Abstract
Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.
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- 2018
- Full Text
- View/download PDF
4. Assessment of the role of genetic variation in the transient neonatal diabetes (TNDM) region on chromosome 6q24 in type 2 diabetes: a comparative genomic and haplotype approach
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Gloyn, AL, MacKay, DJG, Weedon, MN, McCarthy, MI, Walker, M, Hitman, G, Sampson, M, Knight, BA, Hattersley, AT, and Frayling, TM
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- 2016
5. Diagnosis and management of Silver-Russell syndrome: first international consensus statement
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Wakeling, EL, Brioude, F, Lokulo-Sodipe, O, O'Connell, SM, Salem, J, Bliek, J, Canton, APM, Chrzanowska, KH, Davies, JH, Dias, RP, Dubern, B, Elbracht, M, Giabicani, E, Grimberg, A, Gronskov, K, Koelega, Anita, Jorge, AA, Kagami, M, Linglart, A, Maghnie, M, Mohnike, K, Monk, D, Moore, GE, Murray, PG, Ogata, T, Petit, IO, Russo, S, Said, E, Toumba, M, Tumer, Z, Binder, G, Eggermann, T, Harbison, MD, Temple, IK, Mackay, DJG, Netchine, I, Wakeling, EL, Brioude, F, Lokulo-Sodipe, O, O'Connell, SM, Salem, J, Bliek, J, Canton, APM, Chrzanowska, KH, Davies, JH, Dias, RP, Dubern, B, Elbracht, M, Giabicani, E, Grimberg, A, Gronskov, K, Koelega, Anita, Jorge, AA, Kagami, M, Linglart, A, Maghnie, M, Mohnike, K, Monk, D, Moore, GE, Murray, PG, Ogata, T, Petit, IO, Russo, S, Said, E, Toumba, M, Tumer, Z, Binder, G, Eggermann, T, Harbison, MD, Temple, IK, Mackay, DJG, and Netchine, I
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- 2017
6. EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver-Russell and Beckwith-Wiedemann syndrome
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Eggermann, K, Bliek, J, Brioude, F, Algar, E, Buiting, K, Russo, S, Tumer, Z, Monk, D, Moore, G, Antoniadi, T, Macdonald, F, Netchine, I, Lombardi, P, Soellner, L, Begemann, M, Prawitt, D, Maher, ER, Mannens, M, Riccio, A, Weksberg, R, Lapunzina, P, Gronskov, K, Mackay, DJG, Eggermann, T, Eggermann, K, Bliek, J, Brioude, F, Algar, E, Buiting, K, Russo, S, Tumer, Z, Monk, D, Moore, G, Antoniadi, T, Macdonald, F, Netchine, I, Lombardi, P, Soellner, L, Begemann, M, Prawitt, D, Maher, ER, Mannens, M, Riccio, A, Weksberg, R, Lapunzina, P, Gronskov, K, Mackay, DJG, and Eggermann, T
- Abstract
Molecular genetic testing for the 11p15-associated imprinting disorders Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014 and in context with activities of the European Network of Imprinting Disorders (EUCID.net) towards a consensus in diagnostics and management of SRS and BWS, best practice guidelines have now been developed. Members of institutions working in the field of SRS and BWS diagnostics were invited to comment, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from peer-reviewed and published data, as well as observations of the authors in their practice. However, these guidelines can only provide a snapshot of current knowledge at the time of manuscript submission and readers are advised to keep up with the literature.
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- 2016
7. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
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S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. Obrosova, J Fruchart, M Ilic, Björn Eliasson, Gilles Chatellier, M A Martín, D M Kendall, Holger Luthman, V F Varillas, D Maccubbin, Jang S-A., Amalia Gastaldelli, E Salzsieder, P. de Mol, A Yoshida, H D Lindner, D Gostiljac, M Just, Pan C-Y., J M Fujitaki, G Eiermann, K Bergenheim, A D Frick, A Agacdiken, K Varytimiadis, K Cseh, D A Jackson, S Calderari, Dena G. Hernandez, H M Liebich, K Min, F. de Zegher, Bernd Kulzer, K Han, Ulrich A. Müller, D Marrero, H Hatakeyama, René Koopman, Doo H-K., Petr Wohl, P. Sharp, P Forder, Thor Aspelund, N Meneveau, R M Schmülling, R Aubert, Thom Sam., H Youshikawa, M Ankelo, D Bowden, I Kelly, Frédéric Fumeron, M Sartini, Robert S. Sherwin, L Varadhan, A Criscimanna, John Betteridge, V Jelic, M Bartnik, N Lemke, B Ursø, A Bertoldo, A M Owona, H Okochi, L Pérez-Tamajó, S L Monfre, Daniel Brandhorst, K T Legg, Andries J. Smit, Veronica Sancho, Masashi Hirai, C Klein, Paul J. Thornalley, A Chaidaroglou, K Miura, B Zinman, O M Dvoynishnikova, J Plank, Jan Bolinder, C Lush, B Rubi, R Pozzilli, M Bashir, S A Shtandel, F Mosca, A Naskalska, Josef Vcelak, U Sausbier, P Cavaiani, T U Baehring, Michele Solimena, P Formisano, M Rastaldi, Bernard Thorens, J Ruzzin, E Arbit, M. Hori, Torkel B. Brismar, E Soltes Rak, A Filo, P Heinke, Matthew P. Coghlan, M Masotti, I Perevozskaya, K Ahn, I Moules, K Van Dyck, I Goldstein, Z Mathe, G Z Zhao, S Fajardo, J Taylor, S Chrul, J C Pareja, D Hadjidakis, A J Scheen, N Siddiqua, D C Cavan, R Grella, Krabbe S, H J Rochlitz, A E Hinkkanen, W Wilpshaar, Richard Stevens, M Dreyer, S Hara, X Wang, Melania Manco, D Gillen, Magalie A. Ravier, Olli Simell, John C. Lawrence, Kohnert K-D., Agardh C-D., A Berghold, L Kristensen, Grant Sfa., N Gursoy, Leif Groop, N Freemantle, Anja Schweizer, L Pala, Legros J-J., C. Di Pietro, N. Yamamoto, J Magyar, B Nikolovski, H Ikeda, D Lee, Bruce A. Buckingham, A O Wollitzer, I Kennedy, C Ernest, Neville H. McClenaghan, S Tanaka, Asimina Mitrakou, T Heinze, W Kerner, Moeenaldeen Al-Sayed, Charles Thivolet, L Klaff, A Miconi, Cristina Valeri, J. O. Christensen, K. Ekberg, A Jardine, T Endo, X Zhang, D F Child, A Kienitz, D K Seidel, H. Tada, Sylvie Abouna, Cyrus Cooper, Catherine R Chittleborough, Roberta Assaloni, S Corbi, A K Bose, K Ozawa, C Ahn, K A Deans, G Jackowski, Martin Gibson, Patrick McElduff, O A Mojiminiyi, Manuel Serrano-Ríos, O Dupuy, A L Davydov, Iwar Klimes, Sten-Anders Ivarsson, N Ichino, R Matsutomo, E R Smith, A Stefanovska, B Dehmel, K Koniavitou, E Agascioglu, M Hatazaki, J. M. Gibson, T Yada, P Ribaux, M Rupnik, K Fridell, G Scutaru, L Chugunova, Henrietta Mulnier, A Kendereski, H Lehnert, C Billi, M Sobczak, Francisco M-Mj., L K Archibald, S Sukumvanich, David B. Dunger, I. Benke, G Yillar, N Stingemore, J. M. Boavida, Y Shi, Jimmy D. Bell, L Bozzetto, Andrew J. Ahmann, E Jebens, J Keiding, Elena Henkel, Mark Fineman, J F McRae, Carol Forsblom, S Martemucci, Lourdes Ibáñez, P G Prieto, L Ringholm Nielsen, S Pratas, B von Stritzky, Julio Rosenstock, Lee K-W., J Stocks, L J Strow, I Samarguliani, L Wennekes, R Cheung, Abhishek Nag, Roberto Gambino, Y Suleymanoglu, E Murphy, T T Durck, M F Peyrot, Y Unno, Alexander Mayorov, Eleuterio Ferrannini, D. C. Rao, D Neely, H Karunajeewa, J Palmisano, Julia B. Lewis, M Ravid, G Pons, E Junca, P Vexiau, S Sailesh, D K Miloslavskiy, O N Bondarenko, U Smith, S Torri, Constantine Tsigos, Cesario Bianchi, Mattia Locatelli, D Jaquet, Virpi Lindi, M Moroi, M E Tushuizen, P Pelicci, R Scognamiglio, Pal Pacher, S M Thyssen, A Péterfalvi, Y Ho, S Guntram, L Romics, T Nakagami, Clive S. Cockram, Irina Kowalska, K Brodbeck, Gojka Roglic, J. Dörig, Lise Tarnow, Therese Tillin, A López-Alba, Martin Krššák, Moses Elisaf, S Hata, D P Snoeck, D Schmoll, O V Udovichenko, A Scaramuzza, J Paul, John H. 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Lyu, G Rizzo, V V Bogomolov, N Krasova, G M McGuire, Tina Parkner, A Timi, Johann Bauersachs, S Foussas, S A Schreiber, T Monauni, Schwarz Peh., Allenberg, J D Lee, S Dewan, Y G Zheng, D Carroll, E Sarti, C Wollheim, Anna Kaminski, C Menneila, P Bucher, Xu Jyu., Vincent Rigalleau, A Schöpfer, Hans Jörnvall, A Ben Drief, X Jeunemaitre, E Schuster, Chan Slf., S Bilgic, J Coverly, K Szafraniec, Stalenhoef Afh., H Bergert, David I. W. Phillips, J Maksimovic Pavlovic, Sergio E. Starkstein, E Chaim, T Lehmann-Lintz, P Salacone, Tim Armstrong, Ingrid Klöting, C M Frampton, Franco Cavalot, A.K.Azad Khan, H Rose, Marta Letizia Hribal, Jette Kolding Kristensen, H Gröbe, M Nishi, A Vanderplas, Howlett Hsc., L E Bowen, R Malik, A Wu, Charles C. Richardson, Y Li, P G McNally, Yoon K-H., A Baleydier, M J Murphy, P. M. Nilsson, U Lindblad, Sten Madsbad, T Bíró, Riitta Veijola, Charlotte Glümer, Assunta Pandolfi, Lydia Aguilar-Bryan, M Namba, C Franzen, S Lopatriello, David Russel Jones, S. 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Jeffcoate, J Pariès, K Huoponen, Anne Jörns, G Shanmugam, A Tsiavou, S Yoshida, Kim M-J., Annapaula Giulietti, S Paillasson, K Tsuchiya, Divyen K Shah, P Saar, S S Juarez, Stefanie Maxion-Bergemann, J Briody, V Schmitz, C M Pena, J Fernádez-Real, S Naruse, M Kalis, A P Klimenko, X H Chen, H.H. Lervang, G Bock, Mirja Tiikkainen, J Potockova, N Pekcanli, George Dragicevic, Timothy M. Rose, David C. Goff, H Komori, V Vasseur-Delannoy, S Hanley, P Hajos, C W Ahn, Matsuoka T-A., J Burns, Petar M. Seferovic, Yuki Kita, K Lyons, K Kohri, Eleftheria Zeggini, Y Ding, G Belcher, Steven V. Edelman, N Dinççaǧ, Christopher J. Rhodes, Manders Rjf., S Giveon, Dario Iafusco, L Li, M C Ribaudo, Kang S-K., Laurie J. Goodyear, L Martinez, C Vermigli, H Dabire, R Raymond, J de Haan, Christopher J. Groves, Å Norberg, H Jahr, M Gloster, Christopher D. 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Leon, Alberti Gkm., A Opel, S Kokkoris, S B Hong, Philippe Courtois, L Haque, Maria Sörhede Winzell, M C Beauvois, A Szypowska, D Yu, M Gutniak, D Petzinna, B Isomaa, K S Prickett, Maria Felice Brizzi, Pavel Hamet, P J Hammond, K. F. Michelmore, Yumie Takeshita, N Hariharan, Corrado M. Cilio, G Pogatsa, W G Jerome, E Bartley, K Schlembacher, G Blohmó, Guy A. Rutter, Kyung Mook Choi, S. C Tamer, Felix K. Assah, K A Jandeleit-Dahm, M Chan, H Darius, Jørgen F. P. Wojtaszewski, A Papazisi, M Amaya, A Knopff, M Tadayyon, I J Kim, W Russ, T Myrnäs, M. Tryon, S Poonsatha, Noel Cameron, Kim M-H., Alejandra Tomas, F Homo-Dekarche, G. Di Cianni, M Stotzka, C Solimine, Mikhail Borisovich Antsiferov, H Naserke, M Bianchi-Biscay, J I Lara, Moon C-K., Alain Ktorza, Alison N. Jeffery, V Lilla, Eun Seok Kang, Hanley Ajg., J Widder, R Ratner, C Goretti, P J Weston, J Perkins, V Rasmussen, M Evans, T M Gibson, A Jaffe, S I Chisalita, C Owman, L Hiltunen, E Kakishita, C M Mack, H C Potter, M Femerling, M Desai, M Soinio, K Yang, Patricia L. Brubaker, M Meyer, V Dy, J Berden, R Komers, Milos Adamec, R Petzoldt, Alan G. Robinson, R Stevens, A Doi, A Leunda, Eduard Montanya, Alessandra K Cardozo, N Kraenkel, Claudio Cobelli, U A Mueller, S Yamashiro, B R Gedulin, G Francisco, J Dennenmoser, Lesch K-P., Martin G. Bischof, M Ichita, C Fernandes, Jochen Hampe, S Kern, D Kelly, E Zeender, P Perna, J D Best, A C Calkin, Vivian Fonseca, J Prestle, D G Parkes, Satish K. Garg, T Burrell, B M Fischer, D Kruger, J S Skinner, Lin T-M., Jozef Ukropec, Maria Jeziorska, K Arii, David D. D’Alessio, M B Gomes, L Quandt, I Fragaki, M C Brindisi, A Gladkih, E Kitsou, S Di Cola, T Iwasaki, Peter Diem, T Lakka, V V Popova, G Lee, Hannah J. 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Cavanagh, Allen Taylor, M Balabolkin, G Schreier, E Stern, J Lips, V Serban, G Sparacino, Roser Casamitjana, Aine McKillop, I Groza, E Bernal, Kathleen M Gillespie, T Ledet, A Garzaniti, F Hawkins, K M Tushaus, C Renaudin, Christina Maier, A Dormi, A Ubertalli, Inge Tetens, M Ostojic, E Pierre-Justin, A Bhushan, E Ur, L I Jeltova, Tilo Moede, E Tibiriça, Zoran Gucev, Knoch K-P., G Pizzolanti, A M Şengül, T P Degenhardt, Cristina Lencioni, M Fitchet, E Santini, E Devangelio, C Panaite, Y I Karachentsev, S B Solerte, Christos Manes, M Lipka, C H Teng, P Mrak, G Fegan, R C Milton, M Negrean, Astrid Plamboeck, L Patti, M Houk, Ritva Kauppinen-Mäkelin, Christoph F Ebenbichler, O Sysoyeva, Frantisek Saudek, H Wysocki, Robert A. Rizza, J Altirriba, Bjørn Richelsen, L. Lam, Rémy Burcelin, A Antsaklis, G Galimberti, R. de Vries, A Lewin, Marcia A. 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Vingrys, S Habu, Mariella Trovati, H Sobajima, Pierre Lecomte, Kim T-H., D Virsaladze, M Oprean, F Pullen, A Rußmann, G J Bruining, Martina Düfer, Wen Xu, Min Y-K., Norman E Cameron, Gianfranco Pagano, K Harley, M Su, J P Le Berre, Sian Ellard, S Howard, D Russell-Jones, Z Li, S Carpenter, E L Thomas, W Tang, Lee M-S., N Ubrich, M. M. McMahon, G Vassilikos, N Brossa, M S Joergensen, S Smith, A Vania, Y Laurent, S Basir, A Freudenthaler, Sally M. Marshall, D Niedermayer, V I Pankiv, J Mentel, S Pruna, J M Pou Torelló, Y Ito, G Chrysos, Werner Kramer, Hironori Yamasaki, L Bowman, F Palumbo, P Ruth, G Lankas, Z H Liao, D Park, W Otter, C Montrone, Sevasti Zervou, Jennifer L. Wilkinson-Berka, Bo Feldt-Rasmussen, I Banu, Paolo Sbraccia, Bani Mukhopadhyay, Mark E. Cooper, M Kidron, Pål R. Njølstad, A M Jonsdottir, M R Burge, G Valpiani, Yutaka Oiso, David J. 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Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
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0303 health sciences ,medicine.medical_specialty ,business.industry ,EASD ,Endocrinology, Diabetes and Metabolism ,Human physiology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Family medicine ,Internal Medicine ,Medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2004
8. Transient Neonatal Diabetes, ZFP57, and Hypomethylation of Multiple Imprinted Loci A detailed follow-up
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Boonen, SE, Mackay, DJG, Hahnemann, JMD, Docherty, L, Gronskov, K, Lehmann, A, Larsen, LG, Haemers, AP, Kockaerts, Y, Dooms, L, Dung, CV, Ngoc, CTB, Phuong, BN, Kordonouri, O, Sundberg, F, Dayanikli, P, Puthi, V, Acerini, C, Massoud, AF, Tumer, Z, Temple, IK, Boonen, SE, Mackay, DJG, Hahnemann, JMD, Docherty, L, Gronskov, K, Lehmann, A, Larsen, LG, Haemers, AP, Kockaerts, Y, Dooms, L, Dung, CV, Ngoc, CTB, Phuong, BN, Kordonouri, O, Sundberg, F, Dayanikli, P, Puthi, V, Acerini, C, Massoud, AF, Tumer, Z, and Temple, IK
- Abstract
OBJECTIVE: Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because it has impact on the phenotype and recurrence risk for families. We have determined the genotype, phenotype, and epigenotype of the first 10 families to alert health professionals to this newly described genetic subgroup of diabetes. RESEARCH DESIGN AND METHODS: The 10 families (14 homozygous/compound heterozygous individuals) with ZFP57 mutations were ascertained through TNDM1 diagnostic testing. ZFP57 was sequenced in probands and their relatives, and the methylation levels at multiple maternally and paternally imprinted loci were determined. Medical and family histories were obtained, and clinical examination was performed. RESULTS: The key clinical features in probands were transient neonatal diabetes, intrauterine growth retardation, macroglossia, heart defects, and developmental delay. However, the finding of two homozygous relatives without diabetes and normal intelligence showed that the phenotype could be very variable. The epigenotype always included total loss of methylation at the TNDM1 locus and reproducible combinations of differential hypomethylation at other maternally imprinted loci, including tissue mosaicism. CONCLUSIONS: There is yet no clear genotype-epigenotype-phenotype correlation to explain the variable clinical presentation, and this results in difficulties predicting the prognosis of affected individuals. However, many cases have a more severe phenotype than seen in other causes of TNDM1. Further cases and global epigenetic testing are needed to clarify this.
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- 2013
9. Early onset non insulin dependent diabetes mellitus (NIDDM) - a link with paternal duplication of 6q24 and transient neonatal diabetes mellitus (TNDM)
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Temple, Ik, Gardner, Rj, Mackay, Djg, Robinson, Do, Valerio, G., Franzese, A., Barber, Jck, and Shield, Jph
- Published
- 1999
10. Incidence of neonatal diabetes in Austria -- calculation based on the Austrian Diabetes Register.
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Wiedemann B, Schober E, Waldhoer T, Koehle J, Flanagan SE, Mackay DJG, Steichen E, Meraner D, Zimmerhackl L, Hattersley AT, Ellard S, and Hofer S
- Abstract
Background: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes which is diagnosed in the first 6 months of life. Several studies in the last few years provide information on genetic causes for NDM. Objective: The aim of this study was to identify all patients with diabetes in the first 6 months of life through the Austrian Diabetes Register, which is available since 1989. A retrospective data analyses was performed to calculate the current incidence of NDM. Subjects and Methods: Ten patients were registered with diabetes onset within the first 6 months of life in the Austrian Diabetes Register. Evaluation of detailed clinical data was performed by sending a questionnaire to all diabetes centers. Results: Ten patients from nine different families with NDM were diagnosed in Austria from 1989 until September 2007. Seven patients (one male, six females) had transient NDM (TNDM), three (two males, one female) showed a permanent course [permanent neonatal diabetes mellitus (PNDM)]. One had immunodeficiency, polyendocrinopathy and enteropathy X-linked (IPEX) syndrome and another showed aplasia of the pancreas; no genetic etiology was found in the third case. In three out of seven patients with a transient course of NDM a genetic diagnosis was possible. Two female siblings had activating point mutations in the ABCC8 gene, although one patient had paternal uniparental isodisomy of chromosome 6q24. One patient's family did not consent to genetic testing. Conclusions: The incidence of NDM in Austria is 1/160 949, with an incidence of 1/ 536 499 for PNDM and 1/229 928 for TNDM. [ABSTRACT FROM AUTHOR]
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- 2010
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11. Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.
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Temple IK, Gardner RJ, Mackay DJG, Barber JCK, Robinson DO, Shield JPH, Temple, I K, Gardner, R J, Mackay, D J, Barber, J C, Robinson, D O, and Shield, J P
- Abstract
Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon after birth, resolves by 18 months, and predisposes to diabetes later in life. A total of 30 patients were ascertained and investigated for aberrations of chromosome 6. A genotype/phenotype study was also performed. Genotypically, these patients can be classified into 4 etiologic groups. Group 1 had paternal uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical twins). Group 2 had a duplication involving chromosome band 6q24, which was paternal in origin where tested (4 sporadic cases and 7 familial cases from 2 families). Group 3 consisted of 1 patient with a loss of methylation at a CpG island within the TND critical region (1 sporadic case). Group 4 had no identifiable rearrangement of chromosome 6 (7 sporadic cases). Most patients were growth retarded at birth, presented at a median age of 3 days, and recovered at a median age of 12 weeks. In group 2, 2 relatives of the TND patients who presented with type 2 diabetes and no early history of TND had inherited an identical duplication. An abnormality of chromosome 6 was identified in approximately 70% of sporadic TND cases and in all familial cases. No significant clinical differences were found between the 4 etiological groups. The study has broadened the clinical spectrum of TND to include type 2 diabetes presenting in later life with no neonatal presentation. The findings are consistent with an imprinted gene for diabetes mapping to 6q24, which we predict will have an important function in normal pancreatic development. [ABSTRACT FROM AUTHOR]
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- 2000
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12. Long-term Follow-up of a Late Diagnosed Patient with Temple Syndrome
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Yordanova N, Iotova V, Mackay DJG, Temple IK, Stoyanova S, and Hachmeriyan M
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- Humans, Female, Adolescent, Follow-Up Studies, Genomic Imprinting, Muscle Hypotonia genetics, Muscle Hypotonia diagnosis, Delayed Diagnosis, Growth Disorders genetics, Growth Disorders diagnosis, Growth Disorders drug therapy, Imprinting Disorders, Facies, Chromosomes, Human, Pair 14 genetics
- Abstract
Temple syndrome is a rare imprinting disorder, caused by alterations in the critical imprinted region 14q32 of chromosome 14. It is characterized by pre- and postnatal growth retardation, truncal hypotonia and facial dysmorphism in the neonatal period. We report an 18-year-old girl with a late diagnosis of Temple syndrome presenting with all typical signs and symptoms including small for gestational age at birth, feeding difficulties, muscle hypotonia and delayed developmental milestones, central precocious puberty, truncal obesity and reduced growth. The patient is the second reported in the literature with signs of clinical and biochemical hyperandrogenism and the first treated with Dehydrocortisone
® , with a good response. The clinical diagnosis of this patient was made after long-term follow up at a single center for rare endocrine diseases, and a molecular genetics diagnosis of complete hypomethylation of 14q32 chromosome imprinting center (DLK/GTL2) was recently established. Growth hormone treatment was not given and although precocious puberty was treated in line with standard protocols, her final height remained below the target range. Increased awareness of Temple syndrome and timely molecular diagnosis enables improvement of clinical care of these patients as well as prevention of inherent metabolic consequences., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)- Published
- 2024
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13. Body Composition and Metabolism in Adults With Molecularly Confirmed Silver-Russell Syndrome.
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Lokulo-Sodipe O, Inskip HM, Byrne CD, Child J, Wakeling EL, Mackay DJG, Temple IK, and Davies JH
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- Humans, Male, Female, Adult, Middle Aged, Young Adult, Aged, Bone Density, Blood Glucose metabolism, Blood Glucose analysis, Blood Pressure physiology, Body Composition, Silver-Russell Syndrome genetics
- Abstract
Context: Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long-term outcomes and adult body composition in SRS are limited., Objective: To evaluate body composition and metabolic health in adults with SRS., Methods: This was an observational study of 25 individuals with molecularly confirmed SRS, aged ≥ 18 years, from research facilities across the UK. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey [SWS]). Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured., Results: Twenty-five adults with SRS were included (52% female). The median age was 32.9 years (range, 22.0 to 69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, P < .001). Fat mass index was similar (9.6 vs 7.8, P = .3). Lean mass percentage (51.8% vs 66.2%, P < .001) and lean mass index (13.5 kg/m2 vs 17.3 kg/m2, P < .001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, P < .001; all median values). Total cholesterol was ≥ 5 mmol/L in 52.0%. Triglyceride levels were ≥ 1.7 mmol/L in 20.8%. Fasting blood glucose levels were ≥ 6.1 mmol/L in 25.0%. Hypertension was present in 33.3%., Conclusion: Adults with SRS have an unfavorable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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14. Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.
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Mackay DJG, Gazdagh G, Monk D, Brioude F, Giabicani E, Krzyzewska IM, Kalish JM, Maas SM, Kagami M, Beygo J, Kahre T, Tenorio-Castano J, Ambrozaitytė L, Burnytė B, Cerrato F, Davies JH, Ferrero GB, Fjodorova O, Manero-Azua A, Pereda A, Russo S, Tannorella P, Temple KI, Õunap K, Riccio A, de Nanclares GP, Maher ER, Lapunzina P, Netchine I, Eggermann T, Bliek J, and Tümer Z
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- Humans, Genetic Testing methods, Genomic Imprinting genetics, DNA Methylation genetics
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Background: Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person. Some cases of MLID are caused by trans-acting genetic variants, frequently not in the patients but their mothers, which have counselling implications. There is currently no consensus on the definition of MLID, clinical indications prompting testing, molecular procedures and methods for epigenetic and genetic diagnosis, recommendations for laboratory reporting, considerations for counselling, and implications for prognosis and management. The purpose of this study is thus to cover this unmet need., Methods: A comprehensive literature search was conducted resulting in identification of more than 100 articles which formed the basis of discussions by two working groups focusing on clinical diagnosis (n = 12 members) and molecular testing (n = 19 members). Following eight months of preparations and regular online discussions, the experts from 11 countries compiled the preliminary documentation and determined the questions to be addressed during a face-to-face meeting which was held with the attendance of the experts together with four representatives of patient advocacy organisations., Results: In light of available evidence and expert consensus, we formulated 16 propositions and 8 recommendations as interim guidance for the clinical and molecular diagnosis of MLID., Conclusions: MLID is a molecular designation, and for patients with MLID and atypical phenotypes, we propose the alternative term multi-locus imprinting syndrome. Due to the intrinsic variability of MLID, the guidelines underscore the importance of involving experts from various fields to ensure a confident approach to diagnosis, counselling, and care. The authors advocate for global, collaborative efforts in both basic and translational research to tackle numerous crucial questions that currently lack answers, and suggest reconvening within the next 3-5 years to evaluate the research advancements and update this guidance as needed., (© 2024. The Author(s).)
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- 2024
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15. A case of mosaic deletion of paternally-inherited PLAGL1 and two cases of upd(6)mat add to evidence for PLAGL1 under-expression as a cause of growth restriction.
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Alhendi ASN, Gazdagh G, Lim D, McMullan D, Wright M, Temple IK, Davies JH, and Mackay DJG
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- Infant, Newborn, Humans, Animals, Mice, Transcription Factors genetics, Cell Cycle Proteins genetics, Tumor Suppressor Proteins genetics, Genomic Imprinting genetics, Uniparental Disomy
- Abstract
PLAGL1 is one of a group of imprinted genes, whose altered expression causes imprinting disorders impacting growth, development, metabolism, and behavior. PLAGL1 over-expression causes transient neonatal diabetes mellitus (TNDM type 1) and, based on murine models, under-expression would be expected to cause growth restriction. However, only some reported individuals with upd(6)mat have growth restriction, giving rise to uncertainty about the role of PLAGL1 in human growth. Here we report three individuals investigated for growth restriction, two with upd(6)mat and one with a mosaic deletion of the paternally-inherited allele of PLAGL1. These cases add to evidence of its involvement in pre- and early post-natal human growth., (© 2023 Wiley Periodicals LLC.)
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- 2024
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16. Height and body mass index in molecularly confirmed Silver-Russell syndrome and the long-term effects of growth hormone treatment.
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Lokulo-Sodipe O, Giabicani E, Canton APM, Ferrand N, Child J, Wakeling EL, Binder G, Netchine I, Mackay DJG, Inskip HM, Byrne CD, Temple IK, and Davies JH
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- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Body Height, Body Mass Index, Human Growth Hormone therapeutic use, Silver-Russell Syndrome drug therapy
- Abstract
Objective: Silver-Russell syndrome (SRS) causes short stature. Growth hormone (GH) treatment aims to increase adult height. However, data are limited on the long-term outcomes of GH in patients with molecularly confirmed SRS. This study evaluated height, body mass index (BMI) and GH treatment in molecularly confirmed SRS., Design: An observational study with retrospective data collection., Patients: Individuals with molecularly confirmed SRS aged ≥13 years., Measurements: Data were collected on height, height gain (change in height standard deviation score [SDS] from childhood to final or near-final height), BMI and gain in BMI (from childhood to adulthood) and previous GH treatment., Results: Seventy-one individuals (40 female) were included. The median age was 22.0 years (range 13.2-69.7). The molecular diagnoses: H19/IGF2:IG-DMR LOM in 80.3% (57/71); upd(7)mat in 16.9% (12/71) and IGF2 mutation in 2.8% (2/71). GH treatment occurred in 77.5% (55/71). Total height gain was greater in GH-treated individuals (median 1.53 SDS vs. 0.53 SDS, p = .007), who were shorter at treatment initiation (-3.46 SDS vs. -2.91 SDS, p = .04) but reached comparable heights to GH-untreated individuals (-2.22 SDS vs. -2.74 SDS, p = .7). In GH-treated individuals, BMI SDS was lower at the most recent assessment (median -1.10 vs. 1.66, p = .002) with lower BMI gain (2.01 vs. 3.58, p = .006) despite similar early BMI SDS to GH-untreated individuals (median -2.65 vs. -2.78, p = .3)., Conclusions: These results support the use of GH in SRS for increasing height SDS. GH treatment was associated with lower adult BMI which may reflect improved metabolic health even following discontinuation of therapy., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)
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- 2022
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17. Whole-genome analysis as a diagnostic tool for patients referred for diagnosis of Silver-Russell syndrome: a real-world study.
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Alhendi ASN, Lim D, McKee S, McEntagart M, Tatton-Brown K, Temple IK, Davies JH, and Mackay DJG
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- DNA Methylation, Female, Genomic Imprinting genetics, Humans, Maternal Inheritance, Pregnancy, Uniparental Disomy, Abnormalities, Multiple genetics, Silver-Russell Syndrome diagnosis, Silver-Russell Syndrome genetics
- Abstract
Background: Silver-Russell syndrome (SRS) is an imprinting disorder characterised by prenatal and postnatal growth restriction, but its clinical features are non-specific and its differential diagnosis is broad. Known molecular causes of SRS include imprinting disturbance, single nucleotide variant (SNV), CNV or UPD affecting several genes; however, up to 40% of individuals with a clinical diagnosis of SRS currently receive no positive molecular diagnosis., Methods: To determine whether whole-genome sequencing (WGS) could uncover pathogenic variants missed by current molecular testing, we analysed data of 72 participants recruited to the 100,000 Genomes Project within the clinical category of SRS., Results: In 20 participants (27% of the cohort) we identified genetic variants plausibly accounting for SRS. Coding SNVs were identified in genes including CDKN1C , IGF2 , IGF1R and ORC1 . Maternal-effect variants were found in mothers of five participants, including two participants with imprinting disturbance and one with multilocus imprinting disorder. Two regions of homozygosity were suggestive of UPD involving imprinted regions implicated in SRS and Temple syndrome, and three plausibly pathogenic CNVs were found, including a paternal deletion of PLAGL1 . In 48 participants with no plausible pathogenic variant, unbiased analysis of SNVs detected a potential association with STX4 ., Conclusion: WGS analysis can detect UPD, CNV and SNV and is potentially a valuable addition to diagnosis of SRS and related growth-restricting disorders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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18. A patient with multilocus imprinting disturbance involving hypomethylation at 11p15 and 14q32, and phenotypic features of Beckwith-Wiedemann and Temple syndromes.
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Grosvenor SE, Davies JH, Lever M, Sillibourne J, Mackay DJG, and Temple IK
- Subjects
- DNA Methylation, Genomic Imprinting genetics, Humans, Uniparental Disomy genetics, Beckwith-Wiedemann Syndrome diagnosis, Beckwith-Wiedemann Syndrome genetics, Silver-Russell Syndrome diagnosis, Silver-Russell Syndrome genetics
- Abstract
Beckwith-Wiedemann syndrome (BWS) and Temple syndrome (TS) are classical imprinting disorders (IDs) with nonconfluent clinical features. We report here on a patient with clinical features of both syndromes, in whom epimutations were found at the BWS and TS imprinted regions, consistent with multilocus imprinting disturbance (MLID). This is the first case report of a patient with clinical features of both conditions who was found to have loss of methylation (LOM) of KCNQ1OT1: TSS-DMR (ICR2) in the 11p15 imprinted region associated with BWS and LOM of MEG3: TSS-DMR in the 14q32 imprinted region associated with TS. The report draws attention to the importance of testing for MLID as a cause of atypical clinical presentations of patients with IDs., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
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- 2022
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19. Ongoing Challenges in the Diagnosis of 11p15.5-Associated Imprinting Disorders.
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Mackay DJG and Temple IK
- Subjects
- DNA Methylation, Epigenesis, Genetic, Genomic Imprinting, Humans, Beckwith-Wiedemann Syndrome diagnosis, Beckwith-Wiedemann Syndrome genetics, Silver-Russell Syndrome diagnosis, Silver-Russell Syndrome genetics
- Abstract
The overgrowth disorder Beckwith-Wiedemann syndrome and the growth restriction disorder Silver-Russell syndrome have been described as 'mirror' syndromes, in both their clinical features and molecular causes. Clinically, their nonspecific features, focused around continuous variables of atypical growth, make it hard to set diagnostic thresholds that are pragmatic without potentially excluding some cases. Molecularly, both are imprinting disorders, classically associated with 'opposite' genetic and epigenetic changes to genes on chromosome 11p15, but both are associated with somatic mosaicism as well as an increasing range of alternative (epi)genetic changes to other genes, which make molecular diagnosis an increasingly complex process. In this Current Opinion, we explore how the understanding of Beckwith-Wiedemann syndrome and Silver-Russell syndrome has evolved in recent years, stretching the canonical 'mirror' designations in different ways for the two disorders and how this is changing clinical and molecular diagnosis. We suggest some possible directions of travel toward more timely and stratified diagnosis, so that patients can access the early interventions that are so critical for good outcome., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2022
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20. Experiences of adolescents living with Silver-Russell syndrome.
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Ballard LM, Jenkinson E, Byrne CD, Child JC, Inskip H, Lokulo-Sodipe O, Mackay DJG, Wakeling EL, Davies JH, Temple IK, and Fenwick A
- Subjects
- Adolescent, Disability Evaluation, Dwarfism psychology, Emotions, Female, Humans, Interviews as Topic, Male, Qualitative Research, Resilience, Psychological, Silver-Russell Syndrome diagnosis, Adaptation, Psychological, Fatigue diagnosis, Fatigue etiology, Pain diagnosis, Pain etiology, Silver-Russell Syndrome psychology, Social Stigma
- Abstract
Objective: The psychosocial impact of growing up with Silver-Russell syndrome (SRS), characterised by growth failure and short stature in adulthood, has been explored in adults; however, there are no accounts of contemporary lived experience in adolescents. Such data could inform current healthcare guidance and transition to adult services. We aimed to explore the lived experience of adolescents with SRS., Design/setting/patients: In-depth, semi-structured interviews were conducted between January 2015 and October 2016 with a sample of eight adolescents aged 13-18 (five girls) with genetically confirmed SRS from the UK. Qualitative interviews were transcribed and coded to identify similarities and differences using thematic analysis; codes were then grouped to form overarching themes., Results: We identified four themes from the interview data: (1) the psychosocial challenges of feeling and looking different; (2) pain, disability and fatigue; (3) anticipated stigma; and (4) building resilience and acceptance. Despite adolescents accepting SRS in their lives, they described ongoing psychosocial challenges and anticipated greater problems to come, such as stigma from prospective employers., Conclusions: Adolescents with SRS may experience psychosocial difficulties from as young as 10 years old related to feeling and looking different; pain, disability and fatigue; anticipated stigma; and future challenges around employment. We discuss these findings in relation to recommendations for the care of adolescents with SRS to prepare them for adult life., Competing Interests: Competing interests: JHD has received travel bursaries from Novo Nordisk, SANDOZ, Ferring and Pfizer. HI reports grants from the UK NIHR and UK Medical Research Council (the latter for her salary) during the conduct of the study. OL-S reports grants from the NIHR during the conduct of the study., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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21. Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood.
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Lokulo-Sodipe O, Ballard L, Child J, Inskip HM, Byrne CD, Ishida M, Moore GE, Wakeling EL, Fenwick A, Mackay DJG, Davies JH, and Temple IK
- Subjects
- Adolescent, Adult, Aged, DNA Methylation genetics, Epigenesis, Genetic, Female, Genomic Imprinting genetics, Humans, Male, Middle Aged, Phenotype, Quality of Life, Silver-Russell Syndrome pathology, Uniparental Disomy pathology, Young Adult, Insulin-Like Growth Factor II genetics, RNA, Long Noncoding genetics, Silver-Russell Syndrome genetics, Uniparental Disomy genetics
- Abstract
Background: Silver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%-10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS., Methods: A retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped., Results: The median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤-2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS., Conclusion: Historical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)
- Published
- 2020
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22. The phenotypic variations of multi-locus imprinting disturbances associated with maternal-effect variants of NLRP5 range from overt imprinting disorder to apparently healthy phenotype.
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Sparago A, Verma A, Patricelli MG, Pignata L, Russo S, Calzari L, De Francesco N, Del Prete R, Palumbo O, Carella M, Mackay DJG, Rezwan FI, Angelini C, Cerrato F, Cubellis MV, and Riccio A
- Subjects
- Child, Female, Genome-Wide Association Study, Genomic Imprinting, Humans, Male, Pedigree, Phenotype, Sequence Analysis, DNA, Exome Sequencing, Young Adult, Abortion, Spontaneous genetics, Autoantigens genetics, Beckwith-Wiedemann Syndrome genetics, Loss of Function Mutation, Maternal Inheritance, Mitochondrial Proteins genetics, Nuclear Proteins genetics
- Abstract
Background: A subset of individuals affected by imprinting disorders displays multi-locus imprinting disturbances (MLID). MLID has been associated with maternal-effect variants that alter the maintenance of methylation at germline-derived differentially methylated regions (gDMRs) in early embryogenesis. Pedigrees of individuals with MLID also include siblings with healthy phenotype. However, it is unknown if these healthy individuals have MLID themselves or if their methylation patterns differ from those associated with imprinting disorders, and in general, if MLID affects the clinical phenotype., Methods: We have investigated gDMR methylation by locus-specific and whole-genome analyses in a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child with no clinical diagnosis of imprinting disorder or other pathologies., Results: We detected MLID with different methylation profiles in the BWS-affected and healthy siblings. Whole-exome sequencing demonstrated the presence of novel loss-of-function variants of NLRP5 in compound heterozygosity in the mother. The methylation profiles of the two siblings were compared with those of other cases with MLID and control groups by principal component analysis and unsupervised hierarchical clustering, but while their patterns were clearly separated from those of controls, we were unable to cluster those associated with specific clinical phenotypes among the MLID cases., Conclusion: The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID adds further evidence to the role of this gene in the maintenance of genomic imprinting in early embryos. Furthermore, our results demonstrate that within these pedigrees, MLID can also be present in the progeny with healthy phenotype, indicating that some sort of compensation occurs between altered imprinted loci in these individuals. The analysis of larger cohorts of patients with MLID is needed to formulate more accurate epigenotype-phenotype correlations.
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- 2019
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23. Growth disrupting mutations in epigenetic regulatory molecules are associated with abnormalities of epigenetic aging.
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Jeffries AR, Maroofian R, Salter CG, Chioza BA, Cross HE, Patton MA, Dempster E, Temple IK, Mackay DJG, Rezwan FI, Aksglaede L, Baralle D, Dabir T, Hunter MF, Kamath A, Kumar A, Newbury-Ecob R, Selicorni A, Springer A, Van Maldergem L, Varghese V, Yachelevich N, Tatton-Brown K, Mill J, Crosby AH, and Baple EL
- Subjects
- Abnormalities, Multiple genetics, Adolescent, Adult, Amish genetics, Child, DNA Methylation, DNA Methyltransferase 3A, Face abnormalities, Hematologic Diseases genetics, Humans, Intellectual Disability genetics, Leukemia, Myeloid, Acute genetics, Male, Methyltransferases, Morphogenesis genetics, Syndrome, Vestibular Diseases genetics, Young Adult, Aging genetics, DNA (Cytosine-5-)-Methyltransferases genetics, Epigenesis, Genetic, Growth Disorders genetics, Mutation
- Abstract
Germline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3 alpha ( DNMT3A ) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns in DNMT3A c.2312G > A; p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown-Rahman syndrome (TBRS), their mosaic father, and 15 TBRS patients with distinct pathogenic de novo DNMT3A variants. This defined widespread DNA hypomethylation at specific genomic sites enriched at locations annotated as genes involved in morphogenesis, development, differentiation, and malignancy predisposition pathways. TBRS patients also displayed highly accelerated DNA methylation aging. These findings were most marked in a carrier of the AML-associated driver mutation p.Arg882Cys. Our studies additionally defined phenotype-related accelerated and decelerated epigenetic aging in two histone methyltransferase disorders: NSD1 Sotos syndrome overgrowth disorder and KMT2D Kabuki syndrome growth impairment. Together, our findings provide fundamental new insights into aberrant epigenetic mechanisms, the role of epigenetic machinery maintenance, and determinants of biological aging in these growth disorders., (© 2019 Jeffries et al.; Published by Cold Spring Harbor Laboratory Press.)
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- 2019
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24. Genetic diagnosis of subfertility: the impact of meiosis and maternal effects.
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Gheldof A, Mackay DJG, Cheong Y, and Verpoest W
- Subjects
- Animals, Gene Expression Regulation, Genetic Counseling, Genetic Markers, Genetic Variation, Humans, Maternal Inheritance, Meiosis genetics, Phenotype, Selection, Genetic, Genetic Predisposition to Disease, Genetic Testing methods, Infertility diagnosis, Infertility genetics
- Abstract
During reproductive age, approximately one in seven couples are confronted with fertility problems. While the aetiology is diverse, including infections, metabolic diseases, hormonal imbalances and iatrogenic effects, it is becoming increasingly clear that genetic factors have a significant contribution. Due to the complex nature of infertility that often hints at a multifactorial cause, the search for potentially causal gene mutations in idiopathic infertile couples has remained difficult. Idiopathic infertility patients with a suspicion of an underlying genetic cause can be expected to have mutations in genes that do not readily affect general health but are only essential in certain processes connected to fertility. In this review, we specifically focus on genes involved in meiosis and maternal-effect processes, which are of critical importance for reproduction and initial embryonic development. We give an overview of genes that have already been linked to infertility in human, as well as good candidates which have been described in other organisms. Finally, we propose a phenotypic range in which we expect an optimal diagnostic yield of a meiotic/maternal-effect gene panel., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
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25. Genomic imprinting disorders: lessons on how genome, epigenome and environment interact.
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Monk D, Mackay DJG, Eggermann T, Maher ER, and Riccio A
- Subjects
- Animals, Humans, DNA Methylation, Genetic Diseases, Inborn genetics, Genome, Human, Genomic Imprinting
- Abstract
Genomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development, and its disruption leads to human disease. Imprinting defects can involve isolated or multilocus epigenetic changes that may have no evident genetic cause, or imprinting disruption can be traced back to alterations of cis-acting elements or trans-acting factors that control the establishment, maintenance and erasure of germline epigenetic imprints. Recent insights into the dynamics of the epigenome, including the effect of environmental factors, suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos.
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- 2019
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26. Genome-wide methylation profiling of Beckwith-Wiedemann syndrome patients without molecular confirmation after routine diagnostics.
- Author
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Krzyzewska IM, Alders M, Maas SM, Bliek J, Venema A, Henneman P, Rezwan FI, Lip KVD, Mul AN, Mackay DJG, and Mannens MMAM
- Subjects
- Beckwith-Wiedemann Syndrome genetics, Chromosomes, Human, Pair 11 genetics, Female, Genomic Imprinting, Humans, Male, Oligonucleotide Array Sequence Analysis, Phenotype, Beckwith-Wiedemann Syndrome diagnosis, DNA Methylation, Whole Genome Sequencing methods
- Abstract
Beckwith-Wiedemann syndrome (BWS) is caused due to the disturbance of imprinted genes at chromosome 11p15. The molecular confirmation of this syndrome is possible in approximately 85% of the cases, whereas in the remaining 15% of the cases, the underlying defect remains unclear. The goal of our research was to identify new epigenetic loci related to BWS. We studied a group of 25 patients clinically diagnosed with BWS but without molecular conformation after DNA diagnostics and performed a whole genome methylation analysis using the HumanMethylation450 Array (Illumina).We found hypermethylation throughout the methylome in two BWS patients. The hypermethylated sites in these patients overlapped and included both non-imprinted and imprinted regions. This finding was not previously described in any BWS-diagnosed patient.Furthermore, one BWS patient exhibited aberrant methylation in four maternally methylated regions-IGF1R, NHP2L1, L3MBTL, and ZDBF2-that overlapped with the differentially methylated regions found in BWS patients with multi-locus imprinting disturbance (MLID). This finding suggests that the BWS phenotype can result from MLID without detectable methylation defects in the primarily disease-associated loci (11p15). Another patient manifested small but significant aberrant methylation in disease-associated loci at 11p near H19, possibly confirming the diagnosis in this patient.
- Published
- 2019
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27. Discrepant molecular and clinical diagnoses in Beckwith-Wiedemann and Silver-Russell syndromes.
- Author
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Mackay DJG, Bliek J, Lombardi MP, Russo S, Calzari L, Guzzetti S, Izzi C, Selicorni A, Melis D, Temple K, Maher E, Brioude F, Netchine I, and Eggermann T
- Subjects
- Beckwith-Wiedemann Syndrome diagnosis, Chromosomes, Human, Pair 11 genetics, DNA Methylation, Genetic Predisposition to Disease genetics, Genetic Testing, Humans, Phenotype, Silver-Russell Syndrome diagnosis, Beckwith-Wiedemann Syndrome genetics, Silver-Russell Syndrome genetics
- Abstract
Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two imprinting disorders associated with opposite molecular alterations in the 11p15.5 imprinting centres. Their clinical diagnosis is confirmed by molecular testing in 50-70% of patients. The authors from different reference centres for BWS and SRS have identified single patients with unexpected and even contradictory molecular findings in respect to the clinical diagnosis. These patients clinically do not fit the characteristic phenotypes of SRS or BWS, but illustrate their clinical heterogeneity. Thus, comprehensive molecular testing is essential for accurate diagnosis and appropriate management, to avoid premature clinical diagnosis and anxiety for the families.
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- 2019
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28. Genetics, molar pregnancies and medieval ideas of monstrous births: the lump of flesh in The King of Tars .
- Author
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Goodison N, Mackay DJG, and Temple IK
- Subjects
- Female, History, Medieval, Humans, Hydatidiform Mole genetics, Pregnancy, Hydatidiform Mole history, Literature, Medieval
- Abstract
The medieval English romance The King of Tars gives an account of a birth of a lump of flesh. This has been considered as fantastic and monstrous in past literature, the horrific union of a Christian and Saracen. However, while the text certainly speaks to miscegenation, we propose that this lump of flesh is actually a hydatidiform mole. We trace the hydatidiform mole from antiquity, surrounding it with contextual medieval examples, from theology, history and medicine, that also describe abnormal births as 'lumps of flesh'. By discussing medieval ideas of monsters as a warning sign, we interpret the lump of flesh in terms of abnormal births, seed transmission, parental contribution and sin. Ideas of warning, blame and intervention present themselves as a response to moles both in medieval texts as well as in modern reactions to hydatidiform moles. We explore the epigenetics of hydatidiform moles and relate them to the medieval text. In The King of Tars , the fault for the lump of flesh could reside with either parent; we find that this is also the case in the genetic formation of the hydatidiform mole; we also argue that the epigenetics supports medieval theories of seed transmission., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2019
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29. Lived experience of Silver-Russell syndrome: implications for management during childhood and into adulthood.
- Author
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Ballard LM, Jenkinson E, Byrne CD, Child JC, Davies JH, Inskip H, Lokulo-Sodipe O, Mackay DJG, Wakeling EL, Temple IK, and Fenwick A
- Subjects
- Adult, Child, Disability Evaluation, Fatigue diagnosis, Fatigue etiology, Female, Humans, Male, Needs Assessment, Psychology, Sex Factors, United Kingdom epidemiology, Adaptation, Psychological physiology, Body Height, Dwarfism etiology, Dwarfism physiopathology, Dwarfism psychology, Pain diagnosis, Pain etiology, Silver-Russell Syndrome diagnosis, Silver-Russell Syndrome epidemiology, Silver-Russell Syndrome physiopathology, Silver-Russell Syndrome psychology
- Abstract
Objective: There is limited information on the psychosocial impact of growing up with Silver-Russell syndrome (SRS), characterised by slow growth in utero leading to short stature in adulthood. Such information could aid families in making difficult treatment decisions and guide management strategies for health professionals. We aimed to explore the lived experience of people with SRS across the lifespan., Design/setting/patients: In-depth, semi-structured interviews were conducted between January 2015 and October 2016 with a sample of 15 adults (six women) with genetically confirmed SRS from the UK. Qualitative interviews were transcribed and coded to identify similarities and differences: codes were then grouped to form overarching themes., Results: Four themes were identified from participant accounts: (1) appearance-related concerns extending beyond height; (2) strategies to deal with real and perceived threats; (3) women's experiences of pain, disability and feeling older than their years; and (4) feeling overlooked in romantic relationships. These themes show that other factors, beyond short stature, affect patient well-being and indicate a mismatch between patient need and healthcare provision., Conclusions: Challenges in SRS during childhood and adolescence were central to the psychosocial impact of SRS, and were not limited to height. These challenges, as well as symptoms such as pain and fatigue for women, have not previously been documented. To help individuals with SRS develop strategies to manage psychosocial issues, we recommend clinicians incorporate psychological services as an integral part of multidisciplinary teams managing individuals with SRS during childhood, adolescence and adulthood., Competing Interests: Competing interests: JHD has received travel bursaries from Novo Nordisk, SANDOZ, Ferring and Pfizer. HI reports grants from the UK National Institute for Health Research and UK Medical Research Council (the latter for her salary) during the conduct of the study. OLS reports grants from the National Institute of Health Research during the conduct of the study., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2019
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30. Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring.
- Author
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Begemann M, Rezwan FI, Beygo J, Docherty LE, Kolarova J, Schroeder C, Buiting K, Chokkalingam K, Degenhardt F, Wakeling EL, Kleinle S, González Fassrainer D, Oehl-Jaschkowitz B, Turner CLS, Patalan M, Gizewska M, Binder G, Bich Ngoc CT, Chi Dung V, Mehta SG, Baynam G, Hamilton-Shield JP, Aljareh S, Lokulo-Sodipe O, Horton R, Siebert R, Elbracht M, Temple IK, Eggermann T, and Mackay DJG
- Subjects
- Apoptosis Regulatory Proteins, Beckwith-Wiedemann Syndrome pathology, Chromosomes, Human, Pair 11 genetics, DNA Methylation genetics, Female, Genomic Imprinting genetics, Germ-Line Mutation genetics, Humans, Infant, Newborn, Infant, Newborn, Diseases genetics, Infant, Newborn, Diseases physiopathology, Maternal Inheritance, Pedigree, Pregnancy, Protein-Arginine Deiminase Type 6, Silver-Russell Syndrome physiopathology, Adaptor Proteins, Signal Transducing genetics, Beckwith-Wiedemann Syndrome genetics, Protein-Arginine Deiminases genetics, Silver-Russell Syndrome genetics
- Abstract
Background: Genomic imprinting results from the resistance of germline epigenetic marks to reprogramming in the early embryo for a small number of mammalian genes. Genetic, epigenetic or environmental insults that prevent imprints from evading reprogramming may result in imprinting disorders, which impact growth, development, behaviour and metabolism. We aimed to identify genetic defects causing imprinting disorders by whole-exome sequencing in families with one or more members affected by multilocus imprinting disturbance., Methods: Whole-exome sequencing was performed in 38 pedigrees where probands had multilocus imprinting disturbance, in five of whom maternal variants in NLRP5 have previously been found., Results: We now report 15 further pedigrees in which offspring had disturbance of imprinting, while their mothers had rare, predicted-deleterious variants in maternal effect genes, including NLRP2 , NLRP7 and PADI6 . As well as clinical features of well-recognised imprinting disorders, some offspring had additional features including developmental delay, behavioural problems and discordant monozygotic twinning, while some mothers had reproductive problems including pregnancy loss., Conclusion: The identification of 20 putative maternal effect variants in 38 families affected by multilocus imprinting disorders adds to the evidence that maternal genetic factors affect oocyte fitness and thus offspring development. Testing for maternal-effect genetic variants should be considered in families affected by atypical imprinting disorders., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
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31. Revisiting Wilms tumour surveillance in Beckwith-Wiedemann syndrome with IC2 methylation loss, reply.
- Author
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Brioude F, Hennekam R, Bliek J, Coze C, Eggermann T, Ferrero GB, Kratz C, Bouc YL, Maas SM, Mackay DJG, Maher ER, Mussa A, and Netchine I
- Subjects
- DNA Methylation, Genomic Imprinting, Humans, Methylation, Beckwith-Wiedemann Syndrome genetics, Wilms Tumor genetics
- Published
- 2018
- Full Text
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32. Growth Hormone Improves Short-Term Growth in Patients with Temple Syndrome.
- Author
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Brightman DS, Lokulo-Sodipe O, Searle BA, Mackay DJG, Davies JH, Temple IK, and Dauber A
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Male, Retrospective Studies, Syndrome, Chromosomes, Human, Pair 14 genetics, DNA Methylation, Growth Disorders drug therapy, Growth Disorders genetics, Growth Disorders pathology, Growth Disorders physiopathology, Human Growth Hormone administration & dosage, Uniparental Disomy genetics, Uniparental Disomy pathology, Uniparental Disomy physiopathology
- Abstract
Background/aims: Temple syndrome is an imprinting disorder caused by maternal uniparental disomy of chromosome 14 (mat UPD14), paternal deletion of 14q32 or paternal hypomethylation of the intergenic differentially methylated region (MEG3/DLK1 IG-DMR). Patients with Temple syndrome have pre- and postnatal growth restriction, short stature, hypotonia, small hands and feet and precocious puberty. We sought to determine whether treatment with growth hormone improves growth outcomes in patients with Temple syndrome., Methods: This was a retrospective observational study reviewing the medical records of 14 patients with Temple syndrome, 7 of whom were treated with growth hormone., Results: After 1 year of growth hormone treatment, the height standard deviation score (SDS) increased a median of 1.31 SDS with a median increased height velocity of 5.30 cm/year., Conclusions: These results suggest short-term improvement in height SDS with growth hormone treatment similar to the response in patients treated under the small for gestational age indication. We recommend considering growth hormone therapy in all patients with Temple syndrome who have short stature., (© 2019 S. Karger AG, Basel.)
- Published
- 2018
- Full Text
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33. Human imprinting disorders: Principles, practice, problems and progress.
- Author
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Mackay DJG and Temple IK
- Subjects
- DNA Methylation, Genetic Diseases, Inborn diagnosis, Humans, Mosaicism, Genetic Diseases, Inborn genetics, Genomic Imprinting
- Abstract
Epigenetic regulation orchestrates gene expression with exquisite precision, over a huge dynamic range and across developmental space and time, permitting genomically-homogeneous humans to develop and adapt to their surroundings. Every generation, these epigenetic marks are re-set twice: in the germline, to enable differentiation of sperm and eggs, and at fertilisation, to create the totipotent zygote that then begins growth and differentiation into a new human. A small group of genes evades the second, zygotic wave of epigenetic reprogramming, and these genes retain an epigenetic 'imprint' of the parent from whom they were inherited. Imprinted genes are (as a general rule) expressed from one parental allele only. Some imprinted genes are critical regulators of growth and development, and thus disruption of their normal monoallelic expression causes congenital imprinting disorders, with clinical features impacting growth, development, behaviour and metabolism. Imprinting disorders as a group have characteristics that challenge diagnosis and management, including clinical and molecular heterogeneity, overlapping clinical features, somatic mosaicism, and multi-locus involvement. New insights into the biology and epigenomics of the early embryo offers new clues about the origin and importance of imprinting disorders., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
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