23 results on '"Clauin S"'
Search Results
2. Familial young-onset forms of diabetes related to HNF4A and rare HNF1A molecular aetiologies
- Author
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Claire Carette, Dubois-Laforgue D, Saint-Martin C, Clauin S, Beaufils S, Larger E, Sola A, Mosnier-Pudar H, Timsit J, and Bellanné-Chantelot C
- Subjects
Adult ,Male ,Polymorphism, Genetic ,Genotype ,Molecular Sequence Data ,Diabetes Mellitus, Type 2 ,Hepatocyte Nuclear Factor 4 ,Mutation ,Humans ,Family ,Female ,Hepatocyte Nuclear Factor 1-alpha ,Age of Onset ,Retrospective Studies - Abstract
We have dissected the rare molecular anomalies that may affect hepatocyte nuclear factor-1a (HNF1A) and hepatocyte nuclear factor-4a (HNF4A) in patients with familial young-onset diabetes for whom HNF1A mutations have been excluded by sequence analysis.Eighty-four unrelatedHNF1A-negative patients with diabetes diagnosed before the age of 40 years, a family history of diabetes and the absence of features suggestive of Type 2 diabetes were included. We analysed by sequencing the HNF4A promoter and coding regions, the HNF1A promoter region and specific regions of HNF1A(B) and HNF1A(C) isoforms and searched for large deletions of HNF1A and HNF4A by multiplex ligation-dependent probe amplification (MLPA).We identified five novel HNF4A mutations (5 ⁄ 84, 6%), including four missense and one in-frame deletion, and one mutation of the HNF1A promoter (1 ⁄ 84). Sequence analysis of isoform-specific coding regions of HNF1A did not reveal any mutation. We next identified two whole gene deletions of HNF1A and HNF4A, respectively (2 ⁄ 84, 2.4%).Altogether, the search for rare molecular events in HNF1A and HNF4A led us to elucidate 8 ⁄ 84 (9.5%) of our HNF1A-negative cases.This study shows that genetic aetiologies remain to be elucidated in familial young-onset diabetes. It also highlights the difficulty of the differential diagnosis with Type 2 diabetes because of the wide clinical expression of monogenic young-onset diabetes and the absence of specific biomarkers.
- Published
- 2010
3. Recurrent reciprocal genomic Rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy
- Author
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Mefford, H.C., Clauin, S., Sharp, A.J., Møller, R.S., Ullmann, R., Kapur, R., Pinkel, D., Cooper, G.M., Ventura, M., Ropers, H.H., Tommerup, Niels, Eichler, E.E., Bellanne-Chantelot, C., Mefford, H.C., Clauin, S., Sharp, A.J., Møller, R.S., Ullmann, R., Kapur, R., Pinkel, D., Cooper, G.M., Ventura, M., Ropers, H.H., Tommerup, Niels, Eichler, E.E., and Bellanne-Chantelot, C.
- Abstract
Udgivelsesdato: 2007/11
- Published
- 2007
4. Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1? (TCF1) promoter region in MODY patients
- Author
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Godart, Fran�ois, primary, Bellann�-Chantelot, Christine, additional, Clauin, S�verine, additional, Gragnoli, Claudia, additional, Abderrahmani, Amar, additional, Blanch�, H�l�ne, additional, Boutin, Philippe, additional, Ch�vre, Jean Claude, additional, Froguel, Philippe, additional, and Bailleul, Bernard, additional
- Published
- 2000
- Full Text
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5. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations.
- Author
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Bellanné-Chantelot C, Chauveau D, Gautier J, Dubois-Laforgue D, Clauin S, Beaufils S, Wilhelm J, Boitard C, Noël L, Velho G, Timsit J, Bellanné-Chantelot, Christine, Chauveau, Dominique, Gautier, Jean-François, Dubois-Laforgue, Danièle, Clauin, Séverine, Beaufils, Sandrine, Wilhelm, Jean-Marie, Boitard, Christian, and Noël, Laure-Hélène
- Abstract
Background: Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene, mostly generating truncated protein. Various phenotypes, including urogenital malformations, are related to HNF-1beta mutations.Objective: To describe clinical and genetic findings in 13 patients with 8 novel HNF-1beta mutations.Design: Multicenter, descriptive study.Setting: 2 departments of diabetes, 1 department of internal medicine, and 1 department of nephrology.Participants: 8 probands with diabetes diagnosed before 40 years of age and nondiabetic kidney disease who were selected independent of their family history of diabetes, and 5 offspring.Measurements: Characteristics of diabetes, renal function and structure, genital tract abnormalities, pancreas structure, insulin secretion, exocrine pancreas function, and liver test results.Results: All mutations, including 5 missense changes, were found in the DNA-binding domain. Cosegregation of the mutation and MODY5 phenotype was observed in 4 families. Occurrence of a de novo mutation was demonstrated in 2 families. Diabetes was present in 10 of 13 mutation carriers. It was clinically overt in 5 participants and found by screening at age 19 to 38 years in 5 participants. Pancreas atrophy was observed in 5 of 6 probands, and pancreas exocrine insufficiency was observed in 6 of 7 probands. Renal involvement, consisting of structural changes and slowly progressive renal failure, was recognized in 9 patients at 18 to 41 years of age. Dysplastic kidneys were found by ultrasonography in 3 fetuses who subsequently showed transient neonatal renal failure. Genital tract abnormalities were present in 5 probands and liver enzyme levels were abnormal in 11 of 13 patients.Limitations: Since the study was small and not population-based, it could not estimate the prevalence of MODY5. Other phenotypes might be associated with HNF-1beta mutations.Conclusions: Maturity-onset diabetes of the young type 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-1beta is warranted, even without a family history of diabetes, in nonobese patients with diabetes and slowly progressive nondiabetic nephropathy, particularly when pancreatic atrophy or genital abnormalities are present. [ABSTRACT FROM AUTHOR]- Published
- 2004
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6. 35th Annual Meeting of the European Association for the Study of Diabetes
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Häring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., McKinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnæs, A. M., Andersen, N. Aa., Osterhoff, M., Möhlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Fürnsinn, C., Nowotny, P., Waldhäusl, W., Roden, M., Neeft, M., Meijer, A. J., Båvenholm, P., Pigon, J., Efendic, S., Kästenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Van Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovská, A., Kasalicky, P., Hosová, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefèbvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valéro, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., de Galan, B., Netea, M. G., Hancu, N., Smits, P., Van der Meer, J. W. M., Osterbye, T., Jørgensen, K. H., Tranum-Jensen, J., Fredman, P., Høy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patanè, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., de Vos, P., Visser, L., de Haan, B. J., Klok, P., van Schilfgaarde, R., Poppema, S., Juang, J.-H., Kuo, C.-H., Hsu, B. R.-S., Nacher, V., Pérez, M., Biarnés, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Büsing, M., Becker, T., Klempnauer, J., Hücking, K., Schmiegel, W. H., Nauck, M. A., Bouček, P., Saudek, F., Adamec, M., Kožitarová, R., Jedináková, T., Vlasáková, Z., Skibová, J., Bartoš, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J.-C., Gillespie, J. S., McMaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Véricel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P.-O., MŞengül, A., Salman, F., Sargrn, M., Özer, E., Karşidaǧ, K., Salman, S., Gedik, S., Satman, İ., Dinççaǧ, N., Yılmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. R., Hayes, J., Simonson, D. C., van der Ven, N. C. W., Lubach, C. H. C., Snoek, F. J., Mollema, E. D., van der Ploeg, H. M., Danne, T., Hoey, H., McGee, H., Fitzgerald, H., Lernmark, B., Thernlund, G., Fredin, K., Hägglöf, B., Lugari, R., Dell’Anna, C., Ugolotti, D., Dei Cas, A., Barilli, A. L., Sard, L., Marani, B., Iotti, M., Zandomeneghi, R., Gnudi, A., Kjems, L. L., Volund, Aa., Toft-Nielsen, M., Damholt, M. B., Hilsted, L., Hughes, T. E., Krarup, T., Holst, J. J., Young, A., Gottlieb, A., Fineman, M., Kolterman, O., Cancelas, J., García-Martínez, J. A., Villanueva-Peñacarrillo, M. L., Valverde, I., Malaisse, W. J., Filipsson, K., Ahrén, B., Balkan, B., Kwasnik, L., Battle, B., Li, X., Egan, J. M., Clocquet, A. R., Elahi, D., Petrella, E., Pricket, K., Petersen, K. F., Sullivan, J. T., Amatruda, J. M., Livingston, J. N., Shulman, G. I., Freyse, E.-J., Knospe, S., Glund, K., Demuth, H.-U., Walker, D., Malik, R. A., Reljanovic, M., Barada, A., Milicevic, Z., Tack, Cees J., Goldstein, David S., Van Huysen, C., Stevens, M. J., Cao, X., Sundkvist, G., Dahlin, L.-B., Eriksson, K.-F., Rosén, I., Lattimer, S. A., Sima, A. A. F., Sullivan, K., Shaw, J. E., de Courten, M. P., Zimmet, P. Z., Gourdy, P., Ruidavets, J. B., Arveiler, D., Amouyel, Ph., Bingham, A., Tauber, J. P., Lam, K. S. L., Wat, N. M. S., Lam, T. H., Janus, E. D., de Pablos, P., Rodriguez, F., Martínez, J., Sánchez, V., Santana, C., García, I., Macías, A., Levin, K., Hother-Nielsen, O., Henriksen, J. E., Beck-Nielsen, H., Brechtel, K., Machann, J., Koch, M., Nielsen, M., Löblein, K., Becker, R., Denignger, M., Renn, W., Machicao, F., Claussen, C. D., Schick, F., Diraison, F., Moulin, P., Beylot, M., Thams, P., Capito, K., Eliasson, Lena, Barg, Sebastian, Göpel, Sven, Kanno, Takahiro, Renström, Erik, Meda, P., Charollais, A., Gjnovci, A., Calabrese, A., Wonkam, A., Caton, D., Wisznievski, L., Serre, V., Cogne, F., Bauquis, J., Bosco, D., Huarte, J., Herrera, P., Gotfredsen, C. F., Vessby, B., Manuel y Keenoy, B., Engelen, W., Vertommen, J., Schrans, S., Louheranta, A., Lindström, J., Tuomilehto, J., Segal, K. R., Heymsfield, S., Hauptman, J., Boldrin, M., Lucas, C., Pandolfi, A., Cetrullo, D., Polishchuck, R., Alberta, M., Pellegrini, G., Calafiore, A., Vitacolonna, E., Capani, F., Consoli, A., Halleux, C. M., Gillot, E. F., Brichard, S. M., Van der Planken, M., Corthouts, B., Peiffer, F., Scholten, D., Walke, M., Assert, R., Pirags, V., Pedula, K. L., Hillier, T. A., Brown, J. B., Santini, S. A., Marra, G., Cotroneo, P., Manto, A., Di Leo, M. A. S., Di Gregorio, S., Tordi, A., Pitocco, D., Ruotolo, V., Ghirlanda, G., Temelkova-Kurktschiev, T., Schaper, F., Koehler, C., Henkel, E., Hanefeld, M., Mancini, L., Citterio, F., Cotroneo, A., Ceroone, S., Castagneto, M., Rajbhandari, S. M., Dent, M. T., Plater, M. E., Harris, N. D., Tesfaye, S., Ward, J. D., Dupuy, O., Mayaudon, H., Lecoules, S., Bauduceau, B., Palou, M., Farret, O., Molinié, C., Antonelli-Incalzi, R., Fuso, L., Giordano, A., Calcagni, M. L., Todaro, L., Basso, S., Tramaglino, L. M., Troncone, L., Pistelli, R., Guillot, R., Bringuier, A., Porokhov, B., Guillausseau, P. J., Feldmann, G., Zivanic, S., Cizmic, M., Dragojevic, R., Vanovic, M., Borghouts, L. B., van Kranenburg, G. P. J., Schaart, G., Keizer, H. A., Niess, A. M., Dickuth, H. H., Lutz, O., Barbe, P., Calazel-Fournier, C., Hernandez, G., Saint-Martin, F., Galitzky, J., Gonçalves, A. A., da Silva, E. C., Brito, I. J. L., da Silva, C. A., Lawrence, N. J., Kousta, E., Mulnier, H., Penny, A., Millauer, B., Johnston, D. G., Robinson, S., Perriello, G., Pimenta, W., Pampanelli, S., Lucidi, P., Lepore, M., Porcellati, F., Cordoni, M. C., De Feo, P., Bolli, G. B., Sjöstrand, M., Holmäng, A., Lönnroth, P., Hauer, B., Grauer, P., Artzner, S., Lang, R., Stumvoll, M., Monti, L. D., Piatti, P. M., Gemone, F., Valsecchi, G., Magni, M., Barbieri, E., Setola, E., Sandoli, E. P., Galli-Kienle, M., Pontiroli, A. E., Nichols, Gregory A., Brown, Jonathan B., Salzsieder, E., Boltz, H., Ramirez, J. C., Rutscher, A., Fischer, U., Koenig, Ch., Friske, M., Schramm, W., Landgraf, R., Bachmann, W., Bangemann, M., Groeneveld, G., Edvell, Anders, Lindström, Per, Tsiotra, P., Koukourava, A., Raptis, S. A., Tsigos, C., Boutou, E., Triandaffilopoulou, A., Egido, E. M., Rodríguez-Gallardo, J., Gutiérrez, E., García, P., Silvestre, R. A., Marco, J., Khan, Akhtar, Ling, Zong-Chao, Ahren, Bo, Efendic, Suad, Bünting, C., Du, X., Zhi Sui, G., Rösen, P., Koschinsky, T., Kearney, T. M., Sharp, P. S., Lapolla, A., Fedele, D., Martano, L., Garbeglio, M., Seraglia, R., Favretto, D., Traldi, P., Meerwaldt, R., Smit, A. J., Links, Th. P., v. Roon, A. M., Graaf, R., Gans, R. O. B., Deynelİ, O., Ersöz, H. Ö., Gogas, D., Fak, A. 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G., Manti, R., Gallo, M., Molinar Hin, A., Brignardello, E., Boccuzzi, G., Li, Shanfang, Xiang, Kunsan, Zhang, Rugeng, Shangguan, Xinhong, Wu, Jianrong, Donnan, P. T., Broomhall, J., Hunter, K., Morris, A. D., Ioannidis, G., Peppa, M., Rontogianni, E., Kallifronas, M., Lekatsas, I., Chrysanthopoulou, G., Anthopoulos, L., Kesse, M., Thalassinos, N., Neves, C., Medina, J. L., Lopes, F., Yılmaz, M., Güvener, N., Güvener, M., Kocagöz, T., Böke, E., Paşaoglu, I., Bascil Tutuncu, N., Oto, A., Karvonen, M. K., Koulu, M., Pesonen, U., Mercuri, M., Rauramaa, R., Rutter, M. K., Kestevan, P., McComb, J. M., Marshall, S. M., Sobieska, M., Wiktorowicz, K., Kanters, S. D. J. M., Banga, J. D., Algra, A., Frijns, C. J. M., Beutler, J. J., Fijnheer, R., Nicoloff, G., Baydanoff, S., Stanimirova, N., Petrova, Ch., Lario, S., Campistol, J. M., Cases, A., Clària, J., Iñigo, P., Esmatjcs, E., Sármán, B., Tóth, M., Kocsis, I., Somogyi, A., Bumbure, A., Jachimowicz, K., Samson, J., Tomasiak, M., Sobol, A., Stańczyk, L., Watala, C., Stradina, P., Wiśniewska-Jarosińska, M., Marciniak, D., Więcławska, B., Watała, C., Golański, J., Zinnat, R., Mahmud, I., Büyükasik, Yahya, Demiroğlu, H., Szczepanik, A., Skowroński, M., Murawska, A., Meeking, D. R., Allard, S., Munday, J., Chowienczyk, P., Shaw, K. M., Cummings, M. H., Šimková, R., Jirsa, M., Hadoke, P. W. F., McIntyre, C. A., Jones, G. C., Williams, B. C., Elliott, A. I., McKnight, J. A., Pernow, J., Bombonato, G. C., Finucci, G. F., Zotta, L., Senses, V., Ozyazgan, S., Ince, E., Tunçdemir, M., Oztürk, M., Sultuybek, G., Akkan, A. G., Özyazgan, S., Unlücerci, Y., Bekpınar, S., Meyer, M. F., Lee, B. C., Shore, A. C., Humphreys, J. M., Tooke, J. E., Dell’Omo, G., Giovannitti, G., Caricato, F., Mariani, M., Pedrinelli, R., Kiviet-Boehm, C., Schwelling, V., Matthäei, S., Pfohl, M., McInerney, D., Itoh, H., Ohno, T., Katoh, N., Baumgartner-Parzer, S., Artwohl, M., Graier, W., Ludwig, C., Tachi, Y., Bannai, C., Shinohara, M., Shimpuku, H., Ohura, K., Bertacca, A., Sasvári, M., Szaleczki, E., Pusztai, P., Boes, U., Klaus, E., Dittrich, P., Wagner, Z., Wittmann, I., Pótó, L., Wagner, L., Mazák, I., Nagy, J., Feletto, F., Taboga, C., Tonutti, L., Lizzio, S., Russo, A., Selmo, V., Ceriello, A., Lekakis, J., Papamichael, C. M., Stamatelopoulos, K., Stamatelopoulos, S., Yillar, D. O., Gay, M., Lillaz, E., Passaro, A., Vanini, A., Calzoni, F., D’Elia, K., Carantoni, M., Zuliani, G., Fellin, R., Solini, A., Chwatko, G., Bald, E., Dramais, A.-S., Wallemacq, P. E., Vandeleene, B., Ciaria, M. V., Ariano, M., Strom, R., Gibney, J., Weiss, U., Turner, B., O’Gorman, P., Watts, G., Powrie, J., Crook, M., Shaw, K., and Cummings, M.
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- 1999
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7. 35th Annual Meeting of the European Association for the Study of Diabetes : Brussels, Belgium, 28 September-2 October 1999
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Ad Darts Memo, Morris For The Collaboration, Juhl, C., Porksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th, Muller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Bjorn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H-M, Oksanen, L., Tuomainen, T-P, Kontula, K., Salonen, J. T., Dekker, J. M., Boks, P., Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., Macalpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M. Jr, Kozakova, H., Kaas, A., Kofronova, O., Tlaskalova-Hogenova, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sorensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Hasko, G., Szabo, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H-H, Genediab, Study Group, Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabak, A. Gy, Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Canton, A., Burgos, R., Hernandez, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simo, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., Mcdermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y-S, Sternesjo, J., Sandler, S., Chen, M-C, Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Breant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessieres-Lacombe, S., Gedec, Study Group, Tauber, J-P, Home, P. D., Lindholm, A., Riis, A., European Insulin Aspart Study Group, Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Us Dm, Study Group Of Insulin Glargine In Type, Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Hvidore Study group on Childhood Diabetes, Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Ukpds, Group, Steiner, G., Dais, Project Group, Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Verges, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph, Benko, B., Ljubic, S., Turk, Z., Granic, M., Marz, W., Wollschlager, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O Rahilly, S., Hattersley, A. T., Mccarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Siman, C., Wisse, Bert, Gittenberger-De Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ozegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rosc, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Skrha, J., Kvasnicka, J., Kalvodova, B., Hilgertova, J., Schatteman, K., Goossens, F., Scharpe, S., Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Haring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., Mckinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnas, A. M., Andersen, N. Aa, Osterhoff, M., Mohlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Furnsinn, C., Nowotny, P., Waldhausl, W., Roden, M., Neeft, M., Meijer, A. J., Bavenholm, P., Pigon, J., Efendic, S., Kastenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovska, A., Kasalicky, P., Hosova, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefebvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valero, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., Galan, B., Netea, M. G., Hancu, N., Smits, P., Meer, J. W. M., Osterbye, T., Jorgensen, K. H., Tranum-Jensen, J., Fredman, P., Hoy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patane, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., Vos, P., Visser, L., Haan, B. J., Klok, P., Schilfgaarde, R., Poppema, S., Juang, J-H, Kuo, C-H, Hsu, B. R-S, Nacher, V., Perez, M., Biarnes, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Busing, M., Becker, T., Klempnauer, J., Hucking, K., Schmiegel, W. H., Nauck, M. A., Boucek, P., Saudek, F., Adamec, M., Kozitarova, R., Jedinakova, T., Vlasakova, Z., Bartos, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J-C, Gillespie, J. S., Mcmaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Vericel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P-O, Msengul, A., Salman, F., Sargrn, M., Ozer, E., Karsidaǧ, K., Salman, S., Gedik, S., Satman, I., Dinccaǧ, N., Yilmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. R., Hayes, J., Simonson, D. C., Ven, N. C. W., Lubach, C. H. C., Snoek, F. J., Mollema, E. D., Ploeg, H. M., Danne, T., Hoey, H., Mcgee, H., Fitzgerald, H., Lernmark, B., Thernlund, G., Fredin, K., Hagglof, B., Lugari, R., Anna, C., Ugolotti, D., Dei Cas, A., Barilli, A. L., Sard, L., Marani, B., Iotti, M., Zandomeneghi, R., Gnudi, A., Kjems, L. L., Volund, Aa, Toft-Nielsen, M., Damholt, M. B., Hilsted, L., Hughes, T. E., Krarup, T., Holst, J. J., Young, A., Gottlieb, A., Fineman, M., Kolterman, O., Cancelas, J., Garcia-Martinez, J. A., Villanueva-Penacarrillo, M. L., Valverde, I., Malaisse, W. J., Filipsson, K., Ahren, B., Balkan, B., Kwasnik, L., Battle, B., Li, X., Egan, J. M., Clocquet, A. R., Elahi, D., Petrella, E., Pricket, K., Petersen, K. F., Sullivan, J. T., Amatruda, J. M., Livingston, J. N., Shulman, G. I., Freyse, E-J, Knospe, S., Glund, K., Demuth, H-U, Walker, D., Malik, R. A., Reljanovic, M., Barada, A., Milicevic, Z., Tack, Cees J., Croatian Study Group for Diabetic Amyotrophy, Goldstein, David S., Huysen, C., Stevens, M. J., Cao, X., Sundkvist, G., Dahlin, L-B, Eriksson, K-F, Rosen, I., Lattimer, S. A., Sima, A. A. F., Sullivan, K., Shaw, J. E., Courten, M. P., Zimmet, P. Z., Gourdy, P., Ruidavets, J. B., Arveiler, D., Amouyel, Ph, Bingham, A., Tauber, J. P., Lam, K. S. L., Wat, N. M. S., Lam, T. H., Janus, E. D., Pablos, P., Rodriguez, F., Martinez, J., Sanchez, V., Santana, C., Garcia, I., Macias, A., Levin, K., Hother-Nielsen, O., Henriksen, J. E., Beck-Nielsen, H., Brechtel, K., Machann, J., Koch, M., Nielsen, M., Loblein, K., Becker, R., Denignger, M., Renn, W., Machicao, F., Claussen, C. D., Schick, F., Diraison, F., Moulin, P., Beylot, M., Thams, P., Capito, K., Eliasson, Lena, Barg, Sebastian, Gopel, Sven, Kanno, Takahiro, Renstrom, Erik, Meda, P., Charollais, A., Gjnovci, A., Calabrese, A., Wonkam, A., Caton, D., Wisznievski, L., Serre, V., Cogne, F., Bauquis, J., Bosco, D., Huarte, J., Herrera, P., Gotfredsen, C. F., Vessby, B., Kanwu, Study Group, Manuel Y Keenoy, B., Engelen, W., Vertommen, J., Schrans, S., Louheranta, A., Lindstrom, J., Tuomilehto, J., Finnish Diabetes Prevention Study Group, Segal, K. R., Heymsfield, S., Hauptman, J., Boldrin, M., Lucas, C., Pandolfi, A., Cetrullo, D., Polishchuck, R., Alberta, M., Pellegrini, G., Calafiore, A., Vitacolonna, E., Capani, F., Consoli, A., Halleux, C. M., Gillot, E. F., Brichard, S. M., Planken, M., Corthouts, B., Peiffer, F., Scholten, D., Walke, M., Assert, R., Pirags, V., Pedula, K. L., Hillier, T. A., Brown, J. B., Eurodiab, Prospective Complications Study Group, Santini, S. A., Marra, G., Cotroneo, P., Manto, A., Di Leo, M. A. S., Di Gregorio, S., Tordi, A., Pitocco, D., Ruotolo, V., Ghirlanda, G., Temelkova-Kurktschiev, T., Schaper, F., Koehler, C., Henkel, E., Hanefeld, M., Mancini, L., Citterio, F., Cotroneo, A., Ceroone, S., Castagneto, M., Rajbhandari, S. M., Dent, M. T., Plater, M. E., Harris, N. D., Tesfaye, S., Ward, J. D., Dupuy, O., Mayaudon, H., Lecoules, S., Bauduceau, B., Palou, M., Farret, O., Molinie, C., Antonelli-Incalzi, R., Fuso, L., Giordano, A., Calcagni, M. L., Todaro, L., Basso, S., Tramaglino, L. M., Troncone, L., Pistelli, R., Guillot, R., Bringuier, A., Porokhov, B., Guillausseau, P. J., Feldmann, G., Zivanic, S., Cizmic, M., Dragojevic, R., Vanovic, M., Borghouts, L. B., Kranenburg, G. P. J., Schaart, G., Keizer, H. A., Niess, A. M., Dickuth, H. H., Lutz, O., Barbe, P., Calazel-Fournier, C., Hernandez, G., Saint-Martin, F., Galitzky, J., Goncalves, A. A., Da Silva, E. C., Brito, I. J. L., Da Silva, C. A., Lawrence, N. 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8. Maturity Onset Diabetes of the Young 5.
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Bellanné-Chantelot, C., Chauveau, D., Gautier, J. F., Dubois- Laforgue, D., Clauin, S., Beaufils, S., Wilhelm, J. M., Boitard, C., Noël, L. H., Velho, G., and Timsit., J.
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TYPE 2 diabetes ,GENES ,GENETIC mutation ,INSULIN ,TOMOGRAPHY - Abstract
Reports on the study conducted on the maturity-onset diabetes of the young 5 (MODY5). Reduction in insulin production due to mutation in the hepatocyte nuclear factor-1 (HNF-1) gene; Methodology of the study being use of ultrasounds, tomography scans and DNA analysis; Suggestion of MODY5 being an uncommon disease with diverse clinical and genetic findings.
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- 2004
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9. Identification of biallelic germline variants of SRP68 in a sporadic case with severe congenital neutropenia.
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Schmaltz-Panneau B, Pagnier A, Clauin S, Buratti J, Marty C, Fenneteau O, Dieterich K, Beaupain B, Donadieu J, Plo I, and Bellanné-Chantelot C
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- Congenital Bone Marrow Failure Syndromes, Germ Cells, Germ-Line Mutation, Humans, Signal Recognition Particle genetics, Neutropenia congenital, Neutropenia diagnosis, Neutropenia genetics
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- 2021
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10. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.
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Bellanné-Chantelot C, Schmaltz-Panneau B, Marty C, Fenneteau O, Callebaut I, Clauin S, Docet A, Damaj GL, Leblanc T, Pellier I, Stoven C, Souquere S, Antony-Debré I, Beaupain B, Aladjidi N, Barlogis V, Bauduer F, Bensaid P, Boespflug-Tanguy O, Berger C, Bertrand Y, Carausu L, Fieschi C, Galambrun C, Schmidt A, Journel H, Mazingue F, Nelken B, Quah TC, Oksenhendler E, Ouachée M, Pasquet M, Saada V, Suarez F, Pierron G, Vainchenker W, Plo I, and Donadieu J
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- Adolescent, Adult, Apoptosis, Autophagy, Bone Marrow Diseases metabolism, Bone Marrow Diseases pathology, Child, Child, Preschool, Congenital Bone Marrow Failure Syndromes, Exocrine Pancreatic Insufficiency metabolism, Exocrine Pancreatic Insufficiency pathology, Female, Humans, Infant, Infant, Newborn, Lipomatosis metabolism, Lipomatosis pathology, Male, Middle Aged, Neutropenia genetics, Neutropenia metabolism, Neutropenia pathology, Shwachman-Diamond Syndrome, Up-Regulation, Young Adult, Bone Marrow Diseases genetics, Endoplasmic Reticulum Stress, Exocrine Pancreatic Insufficiency genetics, Lipomatosis genetics, Mutation, Neutropenia congenital, Signal Recognition Particle genetics
- Abstract
Congenital neutropenias (CNs) are rare heterogeneous genetic disorders, with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and 1 autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with 7 distinct germ line SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life, and required long-term granulocyte colony-stimulating factor therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n = 5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n = 3). The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation, and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54 -mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54 -mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry., (© 2018 by The American Society of Hematology.)
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- 2018
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11. Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience.
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Poitou C, Francois H, Bellanne-Chantelot C, Noel C, Jacquet A, Clauin S, Beaudreuil S, Damieri H, Hebibi H, Hammoudi Y, Benoit G, Charpentier B, and Durrbach A
- Subjects
- Adult, Central Nervous System Diseases genetics, Cohort Studies, Dental Enamel abnormalities, Dental Enamel surgery, Diabetes Mellitus, Type 2 genetics, Female, Follow-Up Studies, Graft Survival, Hepatocyte Nuclear Factor 1-alpha genetics, Hepatocyte Nuclear Factor 1-beta genetics, Humans, Kidney Diseases, Cystic genetics, Male, Middle Aged, Mutation, Survival Analysis, Central Nervous System Diseases surgery, Diabetes Mellitus, Type 2 surgery, Islets of Langerhans Transplantation physiology, Kidney Diseases, Cystic surgery, Kidney Transplantation physiology
- Abstract
The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)
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- 2012
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12. Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia.
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Kraus MR, Clauin S, Pfister Y, Di Maïo M, Ulinski T, Constam D, Bellanné-Chantelot C, and Grapin-Botton A
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- Animals, Child, Preschool, Exons, Genetic Testing, Humans, Infant, Infant, Newborn, Introns, Kidney pathology, Mice, Protein Structure, Tertiary, Carrier Proteins genetics, Codon, Nonsense, Kidney metabolism, Mutation, Missense, Polycystic Kidney Diseases genetics, RNA-Binding Proteins genetics, Wnt Signaling Pathway genetics
- Abstract
Bicaudal C homologue 1 (Bicc1) knockout in mice causes polycystic kidney disease and pancreas development defects, including a reduction in insulin-producing β-cells and ensuing diabetes. We therefore screened 137 patients with renal abnormalities or association of early-onset diabetes and renal disease for genetic alterations in BICC1. We identified two heterozygous mutations, one nonsense in the first K Homology (KH) domain and one missense in the sterile alpha motif (SAM) domain. In mice, Bicc1 blocks canonical Wnt signaling, mostly via its SAM domain. We show that the human BICC1, similar to its mouse counterpart, blocks canonical Wnt signaling. The nonsense mutation identified results in a complete loss of Wnt inhibitory activity. The point mutation in the SAM domain has a similar effect to a complete SAM domain deletion, resulting in a 22% loss of activity., (© 2011 Wiley Periodicals, Inc.)
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- 2012
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13. Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
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Bidet M, Bellanné-Chantelot C, Galand-Portier MB, Golmard JL, Tardy V, Morel Y, Clauin S, Coussieu C, Boudou P, Mowzowicz I, Bachelot A, Touraine P, and Kuttenn F
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- Abortion, Spontaneous genetics, Adrenal Hyperplasia, Congenital drug therapy, Adrenal Hyperplasia, Congenital genetics, Adult, Chi-Square Distribution, Female, Glucocorticoids therapeutic use, Humans, Mutation, Pedigree, Pregnancy, Adrenal Hyperplasia, Congenital complications, Infertility, Female etiology, Pregnancy Outcome genetics, Steroid 21-Hydroxylase genetics
- Abstract
Objective: In contrast to subfertility often reported in women suffering from the classical form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, fertility in nonclassical CAH (NC-CAH) has been rarely studied. Our objective was to evaluate fertility in NC-CAH women., Material and Methods: We studied 190 NC-CAH women (161 probands + 29 first degree relatives). Only 20 probands had consulted for infertility (12%), either alone or associated with hirsutism or menstrual cycle disorders. The diagnosis was established on post-ACTH 17-hydroxyprogesterone 10 ng/ml or greater and further characterized by CYP21A2 gene analysis., Results: Ninety-five of the 190 women wanted pregnancy (aged 26.7 +/- 8.9 yr); 187 pregnancies occurred in 85 women, which resulted in 141 births in 82 of them. Ninety-nine pregnancies (52.9%) occurred before the diagnosis of NC-CAH (96 spontaneously and three with ovulation inducers) whereas 98 occurred after diagnosis (11 spontaneously and 77 with hydrocortisone treatment); 83% of pregnancies were obtained within 1 yr. The rate of miscarriages was 6.5% for pregnancies obtained with glucocorticoid treatment vs. 26.3% without. Two of the 141 infants (1.5%) were born with classical CAH., Conclusion: Subfertility is mild in NC-CAH. However, the rate of miscarriages is lower in pregnancies occurring with glucocorticoid treatment and argues for treating NC-CAH women wanting pregnancy. In addition, considering the high rate of heterozygotes for CYP21A2 mutations in the general population, it is essential to genotype the partner of patients with a severe mutation to predict the risk of classical CAH and offer genetic counseling.
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- 2010
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14. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism.
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Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL, and Ellard S
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- Humans, Hyperinsulinism complications, Sulfonylurea Receptors, ATP-Binding Cassette Transporters genetics, Diabetes Mellitus genetics, Hyperinsulinism genetics, Insulin-Secreting Cells metabolism, Mutation genetics, Potassium Channels, Inwardly Rectifying genetics, Protein Subunits genetics, Receptors, Drug genetics
- Abstract
The beta-cell ATP-sensitive potassium (K(ATP)) channel is a key component of stimulus-secretion coupling in the pancreatic beta-cell. The channel couples metabolism to membrane electrical events bringing about insulin secretion. Given the critical role of this channel in glucose homeostasis it is therefore not surprising that mutations in the genes encoding for the two essential subunits of the channel can result in both hypo- and hyperglycemia. The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1). It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes. This review focuses on reported mutations in both genes, the spectrum of phenotypes, and the implications for treatment on diagnosing patients with mutations in these genes., ((c) 2008 Wiley-Liss, Inc.)
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- 2009
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15. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy.
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Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, and Bellanne-Chantelot C
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- Adult, Aged, Autopsy, Chromosome Deletion, Epilepsy complications, Female, Fetus abnormalities, Gene Dosage, Gene Duplication, Humans, Kidney Diseases complications, Male, Middle Aged, Nucleic Acid Hybridization, Pedigree, Phenotype, Chromosomes, Human, Pair 17 genetics, Diabetes Mellitus genetics, Epilepsy genetics, Gene Rearrangement genetics, Genetic Predisposition to Disease, Genome, Human, Kidney Diseases genetics
- Abstract
Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three independent events that likely resulted from unequal crossing-over between segmental duplications. One of the microdeletions, identified in a fetus with multicystic dysplastic kidneys, encompasses the TCF2 gene on 17q12, previously shown to be mutated in maturity-onset diabetes, as well as in a subset of pediatric renal abnormalities. Fine-scale mapping of the breakpoints in different patient cohorts revealed a recurrent 1.5-Mb de novo deletion in individuals with phenotypes that ranged from congenital renal abnormalities to maturity-onset diabetes of the young type 5. We also identified the reciprocal duplication, which appears to be enriched in samples from patients with epilepsy. We describe the first example of a recurrent genomic disorder associated with diabetes.
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- 2007
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16. Exonic duplication of the hepatocyte nuclear factor-1beta gene (transcription factor 2, hepatic) as a cause of maturity onset diabetes of the young type 5.
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Carette C, Vaury C, Barthélémy A, Clauin S, Grünfeld JP, Timsit J, and Bellanné-Chantelot C
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- Diabetes Mellitus, Type 2 etiology, Exons, Family Health, Female, Humans, Male, Middle Aged, Pedigree, Phenotype, Diabetes Mellitus, Type 2 genetics, Gene Duplication, Hepatocyte Nuclear Factor 1-beta genetics
- Abstract
Context: Maturity onset diabetes of the young (MODY) type 5 has been described as the association of early-onset diabetes and renal disease. Actually, MODY5 encompasses multiple phenotypes, including nondiabetic progressive renal failure, kidney and genital tract malformations, atypical familial hyperuricemic nephropathy, pancreas atrophy, and liver test abnormalities. The occurrence of MODY5 has been associated with various molecular abnormalities of TCF2, including missense, nonsense, small insertion/deletions, and splice site mutations, as well as large genomic deletions or single exonic deletion of TCF2., Design: Using quantitative multiplex PCR amplification of short fluorescent fragments, we have analyzed the TCF2 gene in a French family of which three relatives presented a MODY5 phenotype. The proband had an extended clinical phenotype, including hyperuricemic nephropathy and early gout, chronic renal failure, renal morphological abnormalities, abnormal liver tests, and diabetes. His son had almost no clinical expression of the disease, whereas his grandson had a restricted but severe renal phenotype present from birth., Results: We show that a duplication of the exon 5 of TCF2 is responsible for the MODY5 phenotypes in this family., Conclusions: Thus, we describe a novel molecular mechanism that may be responsible for MODY5, and we emphasize the wide intrafamilial variability of MODY5 expressivity. These observations suggest that the diagnosis of MODY5 may be raised even in subjects with partial phenotypes. They also confirm that quantitative multiplex PCR amplification of short fluorescent fragments analysis should be the first step of genetic screening in patients with a MODY5 phenotype.
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- 2007
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17. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys.
- Author
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Decramer S, Parant O, Beaufils S, Clauin S, Guillou C, Kessler S, Aziza J, Bandin F, Schanstra JP, and Bellanné-Chantelot C
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- Abortion, Eugenic, Female, Fetal Diseases diagnostic imaging, Glomerular Filtration Rate, Humans, Infant, Newborn, Kidney Diseases, Cystic complications, Kidney Diseases, Cystic diagnostic imaging, Male, Oligohydramnios etiology, Parents, Phenotype, Pregnancy, Ultrasonography, Prenatal, Fetal Diseases genetics, Gene Deletion, Hepatocyte Nuclear Factor 1-beta genetics, Kidney Diseases, Cystic genetics
- Abstract
Prenatal discovery of fetal bilateral hyperechogenic kidneys is very stressful for pregnant women and their family, and accurate diagnosis of the cause of the moderate forms of this pathology is very difficult. Hepatocyte nuclear factor-1beta that is encoded by the TCF2 gene is involved in the embryonic development of the kidneys. Sixty-two pregnancies with fetal bilateral hyperechogenic kidneys including 25 fetuses with inaccurate diagnosis were studied. TCF2 gene anomalies were detected in 18 (29%) of these 62 patients, and 15 of these 18 patients presented a complete heterozygous deletion of the TCF2 gene. Family screening revealed de novo TCF2 anomalies in more than half of the patients. TCF2 anomalies were associated with normal amniotic fluid volume and normal-sized kidneys between -2 and +2 SD in all patients except for two sisters. Antenatal cysts were detected in 11 of 18 patients, unilaterally in eight of 11. After birth, cysts appeared during the first year (17 of 18), and in patients with antenatal cysts, the number increased and developed bilaterally with decreased renal growth. In these 18 patients, the GFR decreased with longer follow-up and was lower in patients with solitary functioning dysplastic kidney. Heterozygous deletion of the TCF2 gene is an important cause of fetal hyperechogenic kidneys in this study and showed to be linked with early disease expression. The renal phenotype and the postnatal evolution were extremely variable and need a prospective long-term follow-up. Extrarenal manifestations are frequent in TCF2-linked pathologies. Therefore, prenatal counseling and follow-up should be multidisciplinary.
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- 2007
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18. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort.
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Ulinski T, Lescure S, Beaufils S, Guigonis V, Decramer S, Morin D, Clauin S, Deschênes G, Bouissou F, Bensman A, and Bellanné-Chantelot C
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Kidney physiopathology, Kidney Diseases, Cystic physiopathology, Kidney Function Tests, Male, Phenotype, Gene Deletion, Hepatocyte Nuclear Factor 1-beta genetics, Kidney abnormalities, Kidney Diseases, Cystic genetics, Point Mutation
- Abstract
The hepatocyte nuclear factor-1beta encoded by the TCF2 gene plays a role for the specific regulation of gene expression in various tissues such as liver, kidney, intestine, and pancreatic islets and is involved in the embryonic development of these organs. TCF2 mutations are known to be responsible for the maturity-onset diabetes of the young type 5 associated with renal manifestations. Several observations have suggested that TCF2 mutations may be involved in restricted renal phenotypes. Eighty children (median age at diagnosis 0.2 yr) with renal cysts, hyperechogenicity, hypoplasia, or single kidneys were studied. Quantitative multiplex PCR amplification of short fluorescence fragments for the search of large genomic rearrangements and sequencing for the detection of point mutations were performed. TCF2 anomalies were detected in one third of patients (25 of 80). The main alteration was the complete deletion of the TCF2 gene detected in 16 patients. Family screening revealed de novo TCF2 anomalies in nine of 17 probands with a high prevalence of deletions (seven of nine). TCF2 anomalies were associated with bilateral renal anomalies (P < 0.001) and bilateral cortical cysts (P < 0.001). However, abnormal renal function, detected in 40% of patients, was independent of the TCF2 genotype. No difference in renal function or severity of renal morphologic lesions was observed between patients with a TCF2 deletion and those with point mutations. In conclusion, TCF2 molecular anomalies are involved in restricted renal phenotype in childhood without alteration of glucose metabolism. These findings have important implications in the diagnosis of patients with renal dysplasia with cysts and their follow-up.
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- 2006
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19. Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5.
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Bellanné-Chantelot C, Clauin S, Chauveau D, Collin P, Daumont M, Douillard C, Dubois-Laforgue D, Dusselier L, Gautier JF, Jadoul M, Laloi-Michelin M, Jacquesson L, Larger E, Louis J, Nicolino M, Subra JF, Wilhem JM, Young J, Velho G, and Timsit J
- Subjects
- Adolescent, Adult, Aged, Alleles, Base Sequence, Chromosome Mapping, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation genetics, Phenotype, Diabetes Mellitus, Type 2 classification, Diabetes Mellitus, Type 2 genetics, Hepatocyte Nuclear Factor 1-beta genetics
- Abstract
Maturity-onset diabetes of the young (MODY) 5 is caused by mutations in the TCF2 gene encoding the transcription factor hepatocyte nuclear factor-1beta. However, in 60% of the patients with a phenotype suggesting MODY5, no point mutation is detected in TCF2. We have hypothesized that large genomic rearrangements of TCF2 that are missed by conventional screening methods may account for this observation. In 40 unrelated patients presenting with MODY5 phenotype, TCF2 was screened for mutations by sequencing. Patients without mutations were then screened for TCF2 rearrangements by the quantitative multiplex PCR of short fluorescent fragments (QMPSF). Among the 40 patients, the overall detection rate was 70%: 18 had point mutations, 9 had whole-gene deletions, and 1 had a deletion of a single exon. Similar phenotypes were observed in patients with mutations and in subjects with large deletions. These results suggest that MODY5 is more prevalent than previously reported, with one-third of the cases resulting from large deletions of TCF2. Because QMPSF is more rapid and cost effective than sequencing, we propose that patients whose phenotype is consistent with MODY5 should be screened first with the QMPSF assay. In addition, other MODY genes should be screened for large genomic rearrangements.
- Published
- 2005
- Full Text
- View/download PDF
20. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register.
- Author
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Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, and Donadieu J
- Subjects
- France epidemiology, Gene Expression, Genotype, Granulocyte Colony-Stimulating Factor therapeutic use, Heterozygote, Humans, Neutropenia drug therapy, Neutropenia epidemiology, Prevalence, Registries, Severity of Illness Index, Leukocyte Elastase genetics, Mutation, Missense, Neutropenia genetics, Neutropenia physiopathology
- Abstract
Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN). To date, 30 different mutations have been reported, but no correlation has been found with the degree of neutropenia. To address this issue, we analyzed the clinical, hematologic, and molecular characteristics of 81 unrelated patients with SCN (n = 54) or CN (n = 27). We identified mutations in 31 patients, two thirds of whom had sporadic forms. Familial cases were consistent with dominant inheritance. Seventeen novel mutations were identified, showing that the mutational spectrum encompasses not only the region encoding the mature enzyme but also the prodomains and promoter region. Genotype-phenotype analysis strongly suggested that ELA2 mutations correlate with more severe expression of neutropenia, specifically in patients diagnosed with SCN. This study underlines the importance of ELA2 molecular screening to identify patients who may be at particular risk of severe bacterial infections and/or acute myeloid leukemia/myelodysplasia. By phenotypic analysis of affected relatives and carriers of the same ELA2 mutations, we showed that the expression of neutropenia in CN and SCN may be either homogeneous or variable according to the type of mutations, suggesting different pathogenetic mechanisms.
- Published
- 2004
- Full Text
- View/download PDF
21. Hepatocyte nuclear factor-1 alpha gene inactivation: cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families.
- Author
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Reznik Y, Dao T, Coutant R, Chiche L, Jeannot E, Clauin S, Rousselot P, Fabre M, Oberti F, Fatome A, Zucman-Rossi J, and Bellanne-Chantelot C
- Subjects
- Adenoma pathology, Adolescent, Adult, Family Health, Female, Genetic Testing, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Humans, Liver pathology, Liver Neoplasms pathology, Male, Middle Aged, Pedigree, Phenotype, Adenoma genetics, DNA-Binding Proteins, Diabetes Mellitus, Type 2 genetics, Liver Neoplasms genetics, Nuclear Proteins, Transcription Factors genetics
- Abstract
Heterozygous germline mutations of the hepatocyte nuclear factor (HNF)-1 alpha are associated with maturity-onset diabetes of the young (MODY)3. Recently, the biallelic inactivation of the HNF-1 alpha gene was reported in liver adenomas. We show the occurrence of liver adenomatosis in six MODY3-affected patients from two unrelated and large families. Liver adenomatosis was characterized by the presence of numerous adenomas within a normal hepatic parenchyma. The HNF-1 alpha hot-spot germline mutation P291fs was identified in the two probands and in 16 relatives from the two families. The six patients affected by liver adenomatosis and diabetes exhibited the mutation. The analysis of liver-cell tumors from two affected patients evidenced the biallelic inactivation of HNF-1 alpha. The familial screening confirmed the clinical heterogeneity of the liver phenotype, from silent liver adenomatosis to fatal hemorrhage. These observations warrant the systematic screening for liver adenomatosis in MODY3 families to prevent its potentially deadly complications. Moreover, such screening may help to determine if a particular mutational spectrum of HNF-1 alpha is associated with liver adenomatosis and to establish its prevalence in this frequent form of diabetes in the young adult.
- Published
- 2004
- Full Text
- View/download PDF
22. Novel mutations in CYP21 detected in individuals with hyperandrogenism.
- Author
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Lajić S, Clauin S, Robins T, Vexiau P, Blanché H, Bellanne-Chantelot C, and Wedell A
- Subjects
- Adolescent, Adult, Animals, COS Cells, Drug Stability, Female, Gene Frequency, Genetic Testing, Humans, Steroid 21-Hydroxylase chemistry, Steroid 21-Hydroxylase metabolism, Hyperandrogenism genetics, Mutation, Steroid 21-Hydroxylase genetics
- Abstract
We studied the functional and structural consequences of two novel missense mutations in CYP21 found in women with hyperandrogenism. The women were predicted to carry mutations by hormonal evaluation, but did not display any of the genotypes commonly associated with congenital adrenal hyperplasia. In one woman the novel mutation V304M was found in homozygous form. After expression in COS-1 cells the mutated enzyme was found to have a residual activity of 46% for conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone compared with the normal enzyme. The V304M variant thus represents the sixth known missense mutation associated with nonclassical disease. A normal degradation pattern for this mutant enzyme indicates that the missense mutation is of functional, rather than structural, importance. The other mutation, G375S, was detected in a young woman with signs of hyperandrogenism, in heterozygous form together with P453S, a mutation known to cause nonclassical congenital adrenal hyperplasia (her genotype was G375S+P453S/wild type). This novel variant almost completely abolished enzyme activity; conversion was 1.6% and 0.7% of normal for 17-hydroxyprogesterone and progesterone, respectively. These results underline the importance of genetic evaluation and counseling in hyperandrogenic women who are predicted to carry congenital adrenal hyperplasia-causing mutations by biochemical tests. It also supports the idea that the heterozygous carrier state for CYP21 mutations can be associated with symptoms of androgen excess in certain susceptible individuals.
- Published
- 2002
- Full Text
- View/download PDF
23. Exhaustive screening of the 21-hydroxylase gene in a population of hyperandrogenic women.
- Author
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Blanché H, Vexiau P, Clauin S, Le Gall I, Fiet J, Mornet E, Dausset J, and Bellanné-Chantelot C
- Subjects
- 17-alpha-Hydroxyprogesterone blood, Adolescent, Adrenal Hyperplasia, Congenital enzymology, Adrenal Hyperplasia, Congenital genetics, Adrenocorticotropic Hormone pharmacology, Adult, Alleles, Base Sequence, Child, Cortodoxone blood, DNA Primers genetics, Female, Genetic Counseling, Genetic Testing, Genotype, Heterozygote, Hirsutism enzymology, Hirsutism genetics, Homozygote, Humans, Middle Aged, Mutation, Phenotype, Polymerase Chain Reaction, Hyperandrogenism enzymology, Hyperandrogenism genetics, Steroid 21-Hydroxylase genetics
- Abstract
21-hydroxylase (21-OH) deficiency accounts for the vast majority of nonclassic (NC) forms of congenital adrenal hyperplasia (CAH), and is associated with symptoms detectable either in childhood (precocious puberty) or sometimes only later in adulthood (hirsutism, acne, amenorrhea). While the severe forms of the disease responsible for salt wasting or simple virilization have been extensively studied, the NC 21-OH deficiency is less well characterized, especially in adults. We studied the 21-OH gene (CYP21) in a population of 69 unrelated hyperandrogenic subjects suspected to be homozygous or heterozygous for NC 21-OH deficiency, based on basal and adrenocorticotrophin (ACTH)-stimulated plasma 17-hydroxyprogesterone (17-OHP, 17-OHPSI) and 21-desoxycortisol (21-DOF, 21-DOFSI) levels. To identify all mutations involved, determination of the whole gene sequence, including exons, exon-intron junctions, and promoter region, was performed, followed by a study of large rearrangements and identification of compound heterozygotes. Alterations were identified in at least one allele of 55 hyperandrogenic subjects. Two NC alterations, Val282Leu and Pro454Ser, were detected in 68% and 7% of the affected alleles, respectively, whereas mutations involved in severe forms were identified in 21% of them. These results document the utility of a molecular diagnosis in hyperandrogenic women suspected of being either heterozygous or homozygous for NC 21-OH deficiency and clearly indicate the importance of genetic counseling in such a population.
- Published
- 1997
- Full Text
- View/download PDF
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