424 results on '"Cirak S."'
Search Results
2. Kongenitale myasthene Syndrome im Erwachsenenalter: Diagnostisch herausfordernd, selten, aber behandelbar
- Author
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Wunderlich, G., Abicht, A., Brunn, A., Daimagüler, H.-S., Schroeter, M., Fink, G. R., Lehmann, H. C., and Cirak, S.
- Published
- 2019
- Full Text
- View/download PDF
3. Progrediente Dysarthrie, Ataxie, schmerzhafte Dysästhesien der Beine und Gedächtnisstörung – was war die Ursache?
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Petry-Schmelzer, J. N., Cirak, S., Kabbasch, C., Fink, G. R., and Wunderlich, G.
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- 2019
- Full Text
- View/download PDF
4. Congenital myopathies – Clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom
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Maggi, L., Scoto, M., Cirak, S., Robb, S.A., Klein, A., Lillis, S., Cullup, T., Feng, L., Manzur, A.Y., Sewry, C.A., Abbs, S., Jungbluth, H., and Muntoni, F.
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- 2013
- Full Text
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5. Stepwise ABC system for classification of any type of genetic variant
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Houge, G., Laner, A., Cirak, S., Leeuw, N. de, Scheffer, H., Dunnen, J.T. den, Houge, G., Laner, A., Cirak, S., Leeuw, N. de, Scheffer, H., and Dunnen, J.T. den
- Abstract
Item does not contain fulltext, The American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) system for variant classification is score based with five classes: benign, likely benign, variant of unknown significance (VUS), likely pathogenic, and pathogenic. Here, we present a variant classification model that can be an add-on or alternative to ACMG classification: A stepwise system that can classify any type of genetic variant (e.g., hypomorphic alleles, imprinted alleles, copy number variants, runs of homozygosity, enhancer variants, and variants related to traits). We call it the ABC system because classification is first functional (A), then clinical (B), and optionally a standard comment that fits the clinical question is selected (C). Both steps A and B have 1-5 grading when knowledge is sufficient, if not, class "zero" is assigned. Functional grading (A) only concerns biological consequences with the stages normal function (1), likely normal function (2), hypothetical functional effect (3), likely functional effect (4), and proven functional effect (5). Clinical grading (B) is genotype-phenotype focused with the stages "right type of gene" (1), risk factor (2), and pathogenic (3-5, depending on penetrance). Both grades are listed for each variant and combined to generate a joint class ranging from A to F. Importantly, the A-F classes are linked to standard comments, reflecting laboratory or national policy. In step A, the VUS class is split into class 0 (true unknown) and class 3 (hypothetical functional effect based on molecular predictions or de novo occurrence), providing a rationale for variant-of-interest reporting when the clinical picture could fit the finding. The system gives clinicians a better guide to variant significance.
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- 2022
6. Mutations in MYH7 cause Multi-minicore Disease (MmD) with variable cardiac involvement
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Cullup, T., Lamont, P.J., Cirak, S., Damian, M.S., Wallefeld, W., Gooding, R., Tan, S.V., Sheehan, J., Muntoni, F., Abbs, S., Sewry, C.A., Dubowitz, V., Laing, N.G., and Jungbluth, H.
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- 2012
- Full Text
- View/download PDF
7. Erratum: Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome (The American Journal of Human Genetics (2018) 103(3) (431–439), (S0002929718302374), (10.1016/j.ajhg.2018.07.010))
- Author
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Ghosh, S. G., Becker, K., Huang, H., Salazar, T. D., Chai, G., Salpietro, V., Al-Gazali, L., Waisfisz, Q., Wang, H., Vaux, K. K., Stanley, V., Manole, A., Akpulat, U., Weiss, M. M., Efthymiou, S., Hanna, M. G., Minetti, C., Striano, P., Pisciotta, L., De Grandis, E., Altmuller, J., Weixler, L., Nurnberg, P., Thiele, H., Yis, U., Okur, T. D., Polat, A. I., Amiri, N., Doosti, M., Karimani, E. G., Toosi, M. B., Haddad, G., Karakaya, M., Wirth, B., van Hagen, J. M., Wolf, N. I., Maroofian, R., Houlden, H., Cirak, S., Gleeson, J. G., Human genetics, Pediatric surgery, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, and Amsterdam Reproduction & Development (AR&D)
- Abstract
(The American Journal of Human Genetics 103, 431–439; September 6, 2018) Lisa Weixler has been added to the author list for her experimental and scientific contributions to the biophysical analysis of wild-type and mutant proteins. Her contributions were already mentioned in the acknowledgments. The authors apologize for initially only listing her in the acknowledgments and for the inconvenience. The author list has been corrected online and appears correctly here, and Lisa Weixler's affiliation is indicated as footnote 3: Center for Molecular Medicine Cologne, Cologne, Germany.
- Published
- 2021
8. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Klionsky, DJ, Abdel-Aziz, AK, Abdelfatah, S, Abdellatif, M, Abdoli, A, Abel, S, Abeliovich, H, Abildgaard, MH, Abudu, YP, Acevedo-Arozena, A, Adamopoulos, IE, Adeli, K, Adolph, TE, Adornetto, A, Aflaki, E, Agam, G, Agarwal, A, Aggarwal, BB, Agnello, M, Agostinis, P, Agrewala, JN, Agrotis, A, Aguilar, PV, Ahmad, ST, Ahmed, ZM, Ahumada-Castro, U, Aits, S, Aizawa, S, Akkoc, Y, Akoumianaki, T, Akpinar, HA, Al-Abd, AM, Al-Akra, L, Al-Gharaibeh, A, Alaoui-Jamali, MA, Alberti, S, Alcocer-Gómez, E, Alessandri, C, Ali, M, Alim Al-Bari, MA, Aliwaini, S, Alizadeh, J, Almacellas, E, Almasan, A, Alonso, A, Alonso, GD, Altan-Bonnet, N, Altieri, DC, Álvarez, ÉMC, Alves, S, Alves da Costa, C, Alzaharna, MM, Amadio, M, Amantini, C, Amaral, C, Ambrosio, S, Amer, AO, Ammanathan, V, An, Z, Andersen, SU, Andrabi, SA, Andrade-Silva, M, Andres, AM, Angelini, S, Ann, D, Anozie, UC, Ansari, MY, Antas, P, Antebi, A, Antón, Z, Anwar, T, Apetoh, L, Apostolova, N, Araki, T, Araki, Y, Arasaki, K, Araújo, WL, Araya, J, Arden, C, Arévalo, M-A, Arguelles, S, Arias, E, Arikkath, J, Arimoto, H, Ariosa, AR, Armstrong-James, D, Arnauné-Pelloquin, L, Aroca, A, Arroyo, DS, Arsov, I, Artero, R, Asaro, DML, Aschner, M, Ashrafizadeh, M, Ashur-Fabian, O, Atanasov, AG, Au, AK, Auberger, P, Auner, HW, Aurelian, L, Autelli, R, Avagliano, L, Ávalos, Y, Aveic, S, Aveleira, CA, Avin-Wittenberg, T, Aydin, Y, Ayton, S, Ayyadevara, S, Azzopardi, M, Baba, M, Backer, JM, Backues, SK, Bae, D-H, Bae, O-N, Bae, SH, Baehrecke, EH, Baek, A, Baek, S-H, Baek, SH, Bagetta, G, Bagniewska-Zadworna, A, Bai, H, Bai, J, Bai, X, Bai, Y, Bairagi, N, Baksi, S, Balbi, T, Baldari, CT, Balduini, W, Ballabio, A, Ballester, M, Balazadeh, S, Balzan, R, Bandopadhyay, R, Banerjee, S, Bánréti, Á, Bao, Y, Baptista, MS, Baracca, A, Barbati, C, Bargiela, A, Barilà, D, Barlow, PG, Barmada, SJ, Barreiro, E, Barreto, GE, Bartek, J, Bartel, B, Bartolome, A, Barve, GR, Basagoudanavar, SH, Bassham, DC, Bast, RC, Basu, A, Batoko, H, Batten, I, Baulieu, EE, Baumgarner, BL, Bayry, J, Beale, R, Beau, I, Beaumatin, F, Bechara, LRG, Beck, GR, Beers, MF, Begun, J, Behrends, C, Behrens, GMN, Bei, R, Bejarano, E, Bel, S, Behl, C, Belaid, A, Belgareh-Touzé, N, Bellarosa, C, Belleudi, F, Belló Pérez, M, Bello-Morales, R, Beltran, JSDO, Beltran, S, Benbrook, DM, Bendorius, M, Benitez, BA, Benito-Cuesta, I, Bensalem, J, Berchtold, MW, Berezowska, S, Bergamaschi, D, Bergami, M, Bergmann, A, Berliocchi, L, Berlioz-Torrent, C, Bernard, A, Berthoux, L, Besirli, CG, Besteiro, S, Betin, VM, Beyaert, R, Bezbradica, JS, Bhaskar, K, Bhatia-Kissova, I, Bhattacharya, R, Bhattacharya, S, Bhattacharyya, S, Bhuiyan, MS, Bhutia, SK, Bi, L, Bi, X, Biden, TJ, Bijian, K, Billes, VA, Binart, N, Bincoletto, C, Birgisdottir, AB, Bjorkoy, G, Blanco, G, Blas-Garcia, A, Blasiak, J, Blomgran, R, Blomgren, K, Blum, JS, Boada-Romero, E, Boban, M, Boesze-Battaglia, K, Boeuf, P, Boland, B, Bomont, P, Bonaldo, P, Bonam, SR, Bonfili, L, Bonifacino, JS, Boone, BA, Bootman, MD, Bordi, M, Borner, C, Bornhauser, BC, Borthakur, G, Bosch, J, Bose, S, Botana, LM, Botas, J, Boulanger, CM, Boulton, ME, Bourdenx, M, Bourgeois, B, Bourke, NM, Bousquet, G, Boya, P, Bozhkov, PV, Bozi, LHM, Bozkurt, TO, Brackney, DE, Brandts, CH, Braun, RJ, Braus, GH, Bravo-Sagua, R, Bravo-San Pedro, JM, Brest, P, Bringer, M-A, Briones-Herrera, A, Broaddus, VC, Brodersen, P, Brodsky, JL, Brody, SL, Bronson, PG, Bronstein, JM, Brown, CN, Brown, RE, Brum, PC, Brumell, JH, Brunetti-Pierri, N, Bruno, D, Bryson-Richardson, RJ, Bucci, C, Buchrieser, C, Bueno, M, Buitrago-Molina, LE, Buraschi, S, Buch, S, Buchan, JR, Buckingham, EM, Budak, H, Budini, M, Bultynck, G, Burada, F, Burgoyne, JR, Burón, MI, Bustos, V, Büttner, S, Butturini, E, Byrd, A, Cabas, I, Cabrera-Benitez, S, Cadwell, K, Cai, J, Cai, L, Cai, Q, Cairó, M, Calbet, JA, Caldwell, GA, Caldwell, KA, Call, JA, Calvani, R, Calvo, AC, Calvo-Rubio Barrera, M, Camara, NO, Camonis, JH, Camougrand, N, Campanella, M, Campbell, EM, Campbell-Valois, F-X, Campello, S, Campesi, I, Campos, JC, Camuzard, O, Cancino, J, Candido de Almeida, D, Canesi, L, Caniggia, I, Canonico, B, Cantí, C, Cao, B, Caraglia, M, Caramés, B, Carchman, EH, Cardenal-Muñoz, E, Cardenas, C, Cardenas, L, Cardoso, SM, Carew, JS, Carle, GF, Carleton, G, Carloni, S, Carmona-Gutierrez, D, Carneiro, LA, Carnevali, O, Carosi, JM, Carra, S, Carrier, A, Carrier, L, Carroll, B, Carter, AB, Carvalho, AN, Casanova, M, Casas, C, Casas, J, Cassioli, C, Castillo, EF, Castillo, K, Castillo-Lluva, S, Castoldi, F, Castori, M, Castro, AF, Castro-Caldas, M, Castro-Hernandez, J, Castro-Obregon, S, Catz, SD, Cavadas, C, Cavaliere, F, Cavallini, G, Cavinato, M, Cayuela, ML, Cebollada Rica, P, Cecarini, V, Cecconi, F, Cechowska-Pasko, M, Cenci, S, Ceperuelo-Mallafré, V, Cerqueira, JJ, Cerutti, JM, Cervia, D, Cetintas, VB, Cetrullo, S, Chae, H-J, Chagin, AS, Chai, C-Y, Chakrabarti, G, Chakrabarti, O, Chakraborty, T, Chami, M, Chamilos, G, Chan, DW, Chan, EYW, Chan, ED, Chan, HYE, Chan, HH, Chan, H, Chan, MTV, Chan, YS, Chandra, PK, Chang, C-P, Chang, C, Chang, H-C, Chang, K, Chao, J, Chapman, T, Charlet-Berguerand, N, Chatterjee, S, Chaube, SK, Chaudhary, A, Chauhan, S, Chaum, E, Checler, F, Cheetham, ME, Chen, C-S, Chen, G-C, Chen, J-F, Chen, LL, Chen, L, Chen, M, Chen, M-K, Chen, N, Chen, Q, Chen, R-H, Chen, S, Chen, W, Chen, X-M, Chen, X-W, Chen, X, Chen, Y, Chen, Y-G, Chen, Y-J, Chen, Y-Q, Chen, ZS, Chen, Z, Chen, Z-H, Chen, ZJ, Cheng, H, Cheng, J, Cheng, S-Y, Cheng, W, Cheng, X, Cheng, X-T, Cheng, Y, Cheng, Z, Cheong, H, Cheong, JK, Chernyak, BV, Cherry, S, Cheung, CFR, Cheung, CHA, Cheung, K-H, Chevet, E, Chi, RJ, Chiang, AKS, Chiaradonna, F, Chiarelli, R, Chiariello, M, Chica, N, Chiocca, S, Chiong, M, Chiou, S-H, Chiramel, AI, Chiurchiù, V, Cho, D-H, Choe, S-K, Choi, AMK, Choi, ME, Choudhury, KR, Chow, NS, Chu, CT, Chua, JP, Chua, JJE, Chung, H, Chung, KP, Chung, S, Chung, S-H, Chung, Y-L, Cianfanelli, V, Ciechomska, IA, Cifuentes, M, Cinque, L, Cirak, S, Cirone, M, Clague, MJ, Clarke, R, Clementi, E, Coccia, EM, Codogno, P, Cohen, E, Cohen, MM, Colasanti, T, Colasuonno, F, Colbert, RA, Colell, A, Čolić, M, Coll, NS, Collins, MO, Colombo, MI, Colón-Ramos, DA, Combaret, L, Comincini, S, Cominetti, MR, Consiglio, A, Conte, A, Conti, F, Contu, VR, Cookson, MR, Coombs, KM, Coppens, I, Corasaniti, MT, Corkery, DP, Cordes, N, Cortese, K, Costa, MDC, Costantino, S, Costelli, P, Coto-Montes, A, Crack, PJ, Crespo, JL, Criollo, A, Crippa, V, Cristofani, R, Csizmadia, T, Cuadrado, A, Cui, B, Cui, J, Cui, Y, Culetto, E, Cumino, AC, Cybulsky, AV, Czaja, MJ, Czuczwar, SJ, D'Adamo, S, D'Amelio, M, D'Arcangelo, D, D'Lugos, AC, D'Orazi, G, da Silva, JA, Dafsari, HS, Dagda, RK, Dagdas, Y, Daglia, M, Dai, X, Dai, Y, Dal Col, J, Dalhaimer, P, Dalla Valle, L, Dallenga, T, Dalmasso, G, Damme, M, Dando, I, Dantuma, NP, Darling, AL, Das, H, Dasarathy, S, Dasari, SK, Dash, S, Daumke, O, Dauphinee, AN, Davies, JS, Dávila, VA, Davis, RJ, Davis, T, Dayalan Naidu, S, De Amicis, F, De Bosscher, K, De Felice, F, De Franceschi, L, De Leonibus, C, de Mattos Barbosa, MG, De Meyer, GRY, De Milito, A, De Nunzio, C, De Palma, C, De Santi, M, De Virgilio, C, De Zio, D, Debnath, J, DeBosch, BJ, Decuypere, J-P, Deehan, MA, Deflorian, G, DeGregori, J, Dehay, B, Del Rio, G, Delaney, JR, Delbridge, LMD, Delorme-Axford, E, Delpino, MV, Demarchi, F, Dembitz, V, Demers, ND, Deng, H, Deng, Z, Dengjel, J, Dent, P, Denton, D, DePamphilis, ML, Der, CJ, Deretic, V, Descoteaux, A, Devis, L, Devkota, S, Devuyst, O, Dewson, G, Dharmasivam, M, Dhiman, R, di Bernardo, D, Di Cristina, M, Di Domenico, F, Di Fazio, P, Di Fonzo, A, Di Guardo, G, Di Guglielmo, GM, Di Leo, L, Di Malta, C, Di Nardo, A, Di Rienzo, M, Di Sano, F, Diallinas, G, Diao, J, Diaz-Araya, G, Díaz-Laviada, I, Dickinson, JM, Diederich, M, Dieudé, M, Dikic, I, Ding, S, Ding, W-X, Dini, L, Dinić, J, Dinic, M, Dinkova-Kostova, AT, Dionne, MS, Distler, JHW, Diwan, A, Dixon, IMC, Djavaheri-Mergny, M, Dobrinski, I, Dobrovinskaya, O, Dobrowolski, R, Dobson, RCJ, Đokić, J, Dokmeci Emre, S, Donadelli, M, Dong, B, Dong, X, Dong, Z, Dorn Ii, GW, Dotsch, V, Dou, H, Dou, J, Dowaidar, M, Dridi, S, Drucker, L, Du, A, Du, C, Du, G, Du, H-N, Du, L-L, du Toit, A, Duan, S-B, Duan, X, Duarte, SP, Dubrovska, A, Dunlop, EA, Dupont, N, Durán, RV, Dwarakanath, BS, Dyshlovoy, SA, Ebrahimi-Fakhari, D, Eckhart, L, Edelstein, CL, Efferth, T, Eftekharpour, E, Eichinger, L, Eid, N, Eisenberg, T, Eissa, NT, Eissa, S, Ejarque, M, El Andaloussi, A, El-Hage, N, El-Naggar, S, Eleuteri, AM, El-Shafey, ES, Elgendy, M, Eliopoulos, AG, Elizalde, MM, Elks, PM, Elsasser, H-P, Elsherbiny, ES, Emerling, BM, Emre, NCT, Eng, CH, Engedal, N, Engelbrecht, A-M, Engelsen, AST, Enserink, JM, Escalante, R, Esclatine, A, Escobar-Henriques, M, Eskelinen, E-L, Espert, L, Eusebio, M-O, Fabrias, G, Fabrizi, C, Facchiano, A, Facchiano, F, Fadeel, B, Fader, C, Faesen, AC, Fairlie, WD, Falcó, A, Falkenburger, BH, Fan, D, Fan, J, Fan, Y, Fang, EF, Fang, Y, Fanto, M, Farfel-Becker, T, Faure, M, Fazeli, G, Fedele, AO, Feldman, AM, Feng, D, Feng, J, Feng, L, Feng, Y, Feng, W, Fenz Araujo, T, Ferguson, TA, Fernández, ÁF, Fernandez-Checa, JC, Fernández-Veledo, S, Fernie, AR, Ferrante, AW, Ferraresi, A, Ferrari, MF, Ferreira, JCB, Ferro-Novick, S, Figueras, A, Filadi, R, Filigheddu, N, Filippi-Chiela, E, Filomeni, G, Fimia, GM, Fineschi, V, Finetti, F, Finkbeiner, S, Fisher, EA, Fisher, PB, Flamigni, F, Fliesler, SJ, Flo, TH, Florance, I, Florey, O, Florio, T, Fodor, E, Follo, C, Fon, EA, Forlino, A, Fornai, F, Fortini, P, Fracassi, A, Fraldi, A, Franco, B, Franco, R, Franconi, F, Frankel, LB, Friedman, SL, Fröhlich, LF, Frühbeck, G, Fuentes, JM, Fujiki, Y, Fujita, N, Fujiwara, Y, Fukuda, M, Fulda, S, Furic, L, Furuya, N, Fusco, C, Gack, MU, Gaffke, L, Galadari, S, Galasso, A, Galindo, MF, Gallolu Kankanamalage, S, Galluzzi, L, Galy, V, Gammoh, N, Gan, B, Ganley, IG, Gao, F, Gao, H, Gao, M, Gao, P, Gao, S-J, Gao, W, Gao, X, Garcera, A, Garcia, MN, Garcia, VE, García-Del Portillo, F, Garcia-Escudero, V, Garcia-Garcia, A, Garcia-Macia, M, García-Moreno, D, Garcia-Ruiz, C, García-Sanz, P, Garg, AD, Gargini, R, Garofalo, T, Garry, RF, Gassen, NC, Gatica, D, Ge, L, Ge, W, Geiss-Friedlander, R, Gelfi, C, Genschik, P, Gentle, IE, Gerbino, V, Gerhardt, C, Germain, K, Germain, M, Gewirtz, DA, Ghasemipour Afshar, E, Ghavami, S, Ghigo, A, Ghosh, M, Giamas, G, Giampietri, C, Giatromanolaki, A, Gibson, GE, Gibson, SB, Ginet, V, Giniger, E, Giorgi, C, Girao, H, Girardin, SE, Giridharan, M, Giuliano, S, Giulivi, C, Giuriato, S, Giustiniani, J, Gluschko, A, Goder, V, Goginashvili, A, Golab, J, Goldstone, DC, Golebiewska, A, Gomes, LR, Gomez, R, Gómez-Sánchez, R, Gomez-Puerto, MC, Gomez-Sintes, R, Gong, Q, Goni, FM, González-Gallego, J, Gonzalez-Hernandez, T, Gonzalez-Polo, RA, Gonzalez-Reyes, JA, González-Rodríguez, P, Goping, IS, Gorbatyuk, MS, Gorbunov, NV, Görgülü, K, Gorojod, RM, Gorski, SM, Goruppi, S, Gotor, C, Gottlieb, RA, Gozes, I, Gozuacik, D, Graef, M, Gräler, MH, Granatiero, V, Grasso, D, Gray, JP, Green, DR, Greenhough, A, Gregory, SL, Griffin, EF, Grinstaff, MW, Gros, F, Grose, C, Gross, AS, Gruber, F, Grumati, P, Grune, T, Gu, X, Guan, J-L, Guardia, CM, Guda, K, Guerra, F, Guerri, C, Guha, P, Guillén, C, Gujar, S, Gukovskaya, A, Gukovsky, I, Gunst, J, Günther, A, Guntur, AR, Guo, C, Guo, H, Guo, L-W, Guo, M, Gupta, P, Gupta, SK, Gupta, S, Gupta, VB, Gupta, V, Gustafsson, AB, Gutterman, DD, H B, R, Haapasalo, A, Haber, JE, Hać, A, Hadano, S, Hafrén, AJ, Haidar, M, Hall, BS, Halldén, G, Hamacher-Brady, A, Hamann, A, Hamasaki, M, Han, W, Hansen, M, Hanson, PI, Hao, Z, Harada, M, Harhaji-Trajkovic, L, Hariharan, N, Haroon, N, Harris, J, Hasegawa, T, Hasima Nagoor, N, Haspel, JA, Haucke, V, Hawkins, WD, Hay, BA, Haynes, CM, Hayrabedyan, SB, Hays, TS, He, C, He, Q, He, R-R, He, Y-W, He, Y-Y, Heakal, Y, Heberle, AM, Hejtmancik, JF, Helgason, GV, Henkel, V, Herb, M, Hergovich, A, Herman-Antosiewicz, A, Hernández, A, Hernandez, C, Hernandez-Diaz, S, Hernandez-Gea, V, Herpin, A, Herreros, J, Hervás, JH, Hesselson, D, Hetz, C, Heussler, VT, Higuchi, Y, Hilfiker, S, Hill, JA, Hlavacek, WS, Ho, EA, Ho, IHT, Ho, PW-L, Ho, S-L, Ho, WY, Hobbs, GA, Hochstrasser, M, Hoet, PHM, Hofius, D, Hofman, P, Höhn, A, Holmberg, CI, Hombrebueno, JR, Yi-Ren Hong, C-WH, Hooper, LV, Hoppe, T, Horos, R, Hoshida, Y, Hsin, I-L, Hsu, H-Y, Hu, B, Hu, D, Hu, L-F, Hu, MC, Hu, R, Hu, W, Hu, Y-C, Hu, Z-W, Hua, F, Hua, J, Hua, Y, Huan, C, Huang, C, Huang, H, Huang, K, Huang, MLH, Huang, R, Huang, S, Huang, T, Huang, X, Huang, YJ, Huber, TB, Hubert, V, Hubner, CA, Hughes, SM, Hughes, WE, Humbert, M, Hummer, G, Hurley, JH, Hussain, S, Hussey, PJ, Hutabarat, M, Hwang, H-Y, Hwang, S, Ieni, A, Ikeda, F, Imagawa, Y, Imai, Y, Imbriano, C, Imoto, M, Inman, DM, Inoki, K, Iovanna, J, Iozzo, RV, Ippolito, G, Irazoqui, JE, Iribarren, P, Ishaq, M, Ishikawa, M, Ishimwe, N, Isidoro, C, Ismail, N, Issazadeh-Navikas, S, Itakura, E, Ito, D, Ivankovic, D, Ivanova, S, Iyer, AKV, Izquierdo, JM, Izumi, M, Jäättelä, M, Jabir, MS, Jackson, WT, Jacobo-Herrera, N, Jacomin, A-C, Jacquin, E, Jadiya, P, Jaeschke, H, Jagannath, C, Jakobi, AJ, Jakobsson, J, Janji, B, Jansen-Dürr, P, Jansson, PJ, Jantsch, J, Januszewski, S, Jassey, A, Jean, S, Jeltsch-David, H, Jendelova, P, Jenny, A, Jensen, TE, Jessen, N, Jewell, JL, Ji, J, Jia, L, Jia, R, Jiang, L, Jiang, Q, Jiang, R, Jiang, T, Jiang, X, Jiang, Y, Jimenez-Sanchez, M, Jin, E-J, Jin, F, Jin, H, Jin, L, Jin, M, Jin, S, Jo, E-K, Joffre, C, Johansen, T, Johnson, GVW, Johnston, SA, Jokitalo, E, Jolly, MK, Joosten, LAB, Jordan, J, Joseph, B, Ju, D, Ju, J-S, Ju, J, Juárez, E, Judith, D, Juhász, G, Jun, Y, Jung, CH, Jung, S-C, Jung, YK, Jungbluth, H, Jungverdorben, J, Just, S, Kaarniranta, K, Kaasik, A, Kabuta, T, Kaganovich, D, Kahana, A, Kain, R, Kajimura, S, Kalamvoki, M, Kalia, M, Kalinowski, DS, Kaludercic, N, Kalvari, I, Kaminska, J, Kaminskyy, 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Y, Oshima, S, Rong, Y, Sluimer, JC, Stallings, CL, and Tong, C-K
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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- 2021
9. Ultra-rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17 hours
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Bamborschke, D., Özdemir, Ö., Kreutzer, M., Motameny, S., Thiele, H., Kribs, A., Dötsch, J., Altmüller, J., Nürnberg, P., and Cirak, S.
- Subjects
Technology Platforms - Abstract
Genetic diseases are a major cause of neonatal morbidity and mortality. The clinical differential diagnosis in severely ill neonates, especially in premature infants, is challenging. Next generation sequencing (NGS) diagnostics is a valuable tool, but the turnaround time is often too long to provide a diagnosis in the time needed for clinical guidance in newborn intensive care units (NICU). To minimize turnaround time, we developed an ultra-rapid whole genome sequencing pipeline and tested it in clinical practice. Our pilot case, was a preterm infant presenting with several crises of dehydration, hypoglycaemia and hyponatremia together with nephrocalcinosis and hypertrophic cardiomyopathy. Whole genome sequencing was performed using a paired-end 2x75bp protocol. Sequencing data were exported after 50 sequencing cycles for a first analysis. After run completion, the rapid-sequencing protocol, a second analysis of the 2 x 75 paired-end run was performed. Both analyses comprised read-mapping and SNP-/indel calling on an on-site Edico Genome DRAGEN server, followed by functional annotation and pathogenicity prediction using in-house scripts. After the first analysis within 17 h, the emergency ultra-rapid protocol identified two novel compound heterozygous variants in the insulin receptor gene (INSR), pathogenic variants in which cause Donohue Syndrome. The genetic diagnosis could be confirmed by detection of hyperinsulinism and patient care adjusted. Nonetheless, we decided to pursue RNA studies, proving the functional effect of the novel splice variant and reduced expression levels of INSR in patients skin fibroblasts.
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- 2021
10. Making sense of missense variants in TTN-related congenital myopathies
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Rees, M., Nikoopour, R., Fukuzawa, A., Kho, A.L., Fernandez-Garcia, M.A., Wraige, E., Bodi, I., Deshpande, C., Özdemir, Ö., Daimagüler, H.S., Pfuhl, M., Holt, M., Brandmeier, B., Grover, S., Fluss, J., Longman, C., Farrugia, M.E., Matthews, E., Hanna, M., Muntoni, F., Sarkozy, A., Phadke, R., Quinlivan, R., Oates, E.C., Schröder, R., Thiel, C, Reimann, J., Voermans, N.C., Erasmus, C.E., Kamsteeg, E.J., Konersman, C., Grosmann, C., McKee, S., Tirupathi, S., Moore, S.A., Wilichowski, E., Hobbiebrunken, E., Dekomien, G., Richard, I., Bergh, P., Domínguez-González, C., Cirak, S., Ferreiro, A., Jungbluth, H., Gautel, M., Rees, M., Nikoopour, R., Fukuzawa, A., Kho, A.L., Fernandez-Garcia, M.A., Wraige, E., Bodi, I., Deshpande, C., Özdemir, Ö., Daimagüler, H.S., Pfuhl, M., Holt, M., Brandmeier, B., Grover, S., Fluss, J., Longman, C., Farrugia, M.E., Matthews, E., Hanna, M., Muntoni, F., Sarkozy, A., Phadke, R., Quinlivan, R., Oates, E.C., Schröder, R., Thiel, C, Reimann, J., Voermans, N.C., Erasmus, C.E., Kamsteeg, E.J., Konersman, C., Grosmann, C., McKee, S., Tirupathi, S., Moore, S.A., Wilichowski, E., Hobbiebrunken, E., Dekomien, G., Richard, I., Bergh, P., Domínguez-González, C., Cirak, S., Ferreiro, A., Jungbluth, H., and Gautel, M.
- Abstract
Contains fulltext : 231686.pdf (Publisher’s version ) (Open Access), Mutations in the sarcomeric protein titin, encoded by TTN, are emerging as a common cause of myopathies. The diagnosis of a TTN-related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and the prevalence of TTN variants in control populations. Here, we present a combined clinico-pathological, genetic and biophysical approach to the diagnosis of TTN-related myopathies and the pathogenicity ascertainment of TTN missense variants. We identified 30 patients with a primary TTN-related congenital myopathy (CM) and two truncating variants, or one truncating and one missense TTN variant, or homozygous for one TTN missense variant. We found that TTN-related myopathies show considerable overlap with other myopathies but are strongly suggested by a combination of certain clinico-pathological features. Presentation was typically at birth with the clinical course characterized by variable progression of weakness, contractures, scoliosis and respiratory symptoms but sparing of extraocular muscles. Cardiac involvement depended on the variant position. Our biophysical analyses demonstrated that missense mutations associated with CMs are strongly destabilizing and exert their effect when expressed on a truncating background or in homozygosity. We hypothesise that destabilizing TTN missense mutations phenocopy truncating variants and are a key pathogenic feature of recessive titinopathies that might be amenable to therapeutic intervention.
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- 2021
11. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).
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Quadrilatero J., Walker D.W., Walker M.J., Walker S.A., Walter J., Wandosell F.G., Wang B., Wang C., Wang C.-Y., Wang D., Wang F., Wang G., Wang H., Wang H.-G., Wang J., Wang K., Wang L., Wang M.H., Wang M., Wang N., Wang P., Wang Q.J., Wang Q., Wang Q.K., Wang Q.A., Wang W.-T., Wang W., Wang X., Wang Y.-Y., Wang Y., Wang Z., Warnes G., Warnsmann V., Watada H., Watanabe E., Watchon M., Wawrzynska A., Weaver T.E., Wegrzyn G., Wehman A.M., Wei H., Wei L., Wei T., Wei Y., Weiergraber O.H., Weihl C.C., Weindl G., Weiskirchen R., Wells A., Wen R.H., Wen X., Werner A., Weykopf B., Wheatley S.P., W... [Ovid has truncated this field to avoid Excel character limitations], Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., Anton Z., Anwar T., Apetoh L., Apostolova N., Araki T., Araki Y., Arasaki K., Araujo W.L., Araya J., Arden C., Arevalo M.-A., Arguelles S., Arias E., Arikkath J., Arimoto H., Ariosa A.R., Armstrong-James D., Arnaune-Pelloquin L., Aroca A., Arroyo D.S., Arsov I., Artero R., Asaro D.M.L., Aschner M., Ashrafizadeh M., Ashur-Fabian O., Atanasov A.G., Au A.K., Auberger P., Auner H.W., Aurelian L., Autelli R., Avagliano L., Avalos Y., Aveic S., Aveleira C.A., Avin-Wittenberg T., Aydin Y., Ayton S., Ayyadevara S., Azzopardi M., Baba M., Backer J.M., Backues S.K., Bae D.-H., Bae O.-N., Bae S.H., Baehrecke E.H., Baek A., Baek S.-H., Baek S.H., Bagetta G., Bagniewska-Zadworna A., Bai H., Bai J., Bai X., Bai Y., Bairagi N., Baksi S., Balbi T., Baldari C.T., Balduini W., Ballabio A., Ballester M., Balazadeh S., Balzan R., Bandopadhyay R., Banerjee S., Banreti A., Bao Y., Baptista M.S., Baracca A., Barbati C., Bargiela A., Barila D., Barlow P.G., Barmada S.J., Barreiro E., Barreto G.E., Bartek J., Bartel B., Bartolome A., Barve G.R., Basagoudanavar S.H., Bassham D.C., Bast R.C., Basu A., Batoko H., Batten I., Baulieu E.E., Baumgarner B.L., Bayry J., Beale R., Beau I., Beaumatin F., Bechara L.R.G., Beck G.R., Beers M.F., Begun J., Behrends C., Behrens G.M.N., Bei R., Bejarano E., Bel S., Behl C., Belaid A., Belgareh-Touze N., Bellarosa C., Belleudi F., Bello Perez M., Bello-Morales R., Beltran J.S.D.O., Beltran S., Benbrook D.M., Bendorius M., Benitez B.A., Benito-Cuesta I., Bensalem J., Berchtold M.W., Berezowska S., Bergamaschi D., Bergami M., Bergmann A., Berliocchi L., Berlioz-Torrent C., Bernard A., Berthoux L., Besirli C.G., Besteiro S., Betin V.M., Beyaert R., Bezbradica J.S., Bhaskar K., Bhatia-Kissova I., Bhattacharya R., Bhattacharya S., Bhattacharyya S., Bhuiyan M.S., Bhutia S.K., Bi L., Bi X., Biden T.J., Bijian K., Billes V.A., Binart N., Bincoletto C., Birgisdottir A.B., Bjorkoy G., Blanco G., Blas-Garcia A., Blasiak J., Blomgran R., Blomgren K., Blum J.S., Boada-Romero E., Boban M., Boesze-Battaglia K., Boeuf P., Boland B., Bomont P., Bonaldo P., Bonam S.R., Bonfili L., Bonifacino J.S., Boone B.A., Bootman M.D., Bordi M., Borner C., Bornhauser B.C., Borthakur G., Bosch J., Bose S., Botana L.M., Botas J., Boulanger C.M., Boulton M.E., Bourdenx M., Bourgeois B., Bourke N.M., Bousquet G., Boya P., Bozhkov P.V., Bozi L.H.M., Bozkurt T.O., Brackney D.E., Brandts C.H., Braun R.J., Braus G.H., Bravo-Sagua R., Bravo-San Pedro J.M., Brest P., Bringer M.-A., Briones-Herrera A., Broaddus V.C., Brodersen P., Brodsky J.L., Brody S.L., Bronson P.G., Bronstein J.M., Brown C.N., Brown R.E., Brum P.C., Brumell J.H., Brunetti-Pierri N., Bruno D., Bryson-Richardson R.J., Bucci C., Buchrieser C., Bueno M., Buitrago-Molina L.E., Buraschi S., Buch S., Buchan J.R., Buckingham E.M., Budak H., Budini M., Bultynck G., Burada F., Burgoyne J.R., Buron M.I., Bustos V., Buttner S., Butturini E., Byrd A., Cabas I., Cabrera-Benitez S., Cadwell K., Cai J., Cai L., Cai Q., Cairo M., Calbet J.A., Caldwell G.A., Caldwell K.A., Call J.A., Calvani R., Calvo A.C., Calvo-Rubio Barrera M., Camara N.O.S., Camonis J.H., Camougrand N., Campanella M., Campbell E.M., Campbell-Valois F.-X., Campello S., Campesi I., Campos J.C., Camuzard O., Cancino J., Candido de Almeida D., Canesi L., Caniggia I., Canonico B., Canti C., Cao B., Caraglia M., Carames B., Carchman E.H., Cardenal-Munoz E., Cardenas C., Cardenas L., Cardoso S.M., Carew J.S., Carle G.F., Carleton G., Carloni S., Carmona-Gutierrez D., Carneiro L.A., Carnevali O., Carosi J.M., Carra S., Carrier A., Carrier L., Carroll B., Carter A.B., Carvalho A.N., Casanova M., Casas C., Casas J., Cassioli C., Castillo E.F., Castillo K., Castillo-Lluva S., Castoldi F., Castori M., Castro A.F., Castro-Caldas M., Castro-Hernandez J., Castro-Obregon S., Catz S.D., Cavadas C., Cavaliere F., Cavallini G., Cavinato M., Cayuela M.L., Cebollada Rica P., Cecarini V., Cecconi F., Cechowska-Pasko M., Cenci S., Ceperuelo-Mallafre V., Cerqueira J.J., Cerutti J.M., Cervia D., Cetintas V.B., Cetrullo S., Chae H.-J., Chagin A.S., Chai C.-Y., Chakrabarti G., Chakrabarti O., Chakraborty T., Chami M., Chamilos G., Chan D.W., Chan E.Y.W., Chan E.D., Chan H.Y.E., Chan H.H., Chan H., Chan M.T.V., Chan Y.S., Chandra P.K., Chang C.-P., Chang C., Chang H.-C., Chang K., Chao J., Chapman T., Charlet-Berguerand N., Chatterjee S., Chaube S.K., Chaudhary A., Chauhan S., Chaum E., Checler F., Cheetham M.E., Chen C.-S., Chen G.-C., Chen J.-F., Chen L.L., Chen L., Chen M., Chen M.-K., Chen N., Chen Q., Chen R.-H., Chen S., Chen W., Chen X.-M., Chen X.-W., Chen X., Chen Y.-G., Chen Y., Chen Y.-J., Chen Y.-Q., Chen Z.S., Chen Z.-H., Chen Z.J., Cheng H., Cheng J., Cheng S.-Y., Cheng W., Cheng X., Cheng X.-T., Cheng Y., Cheng Z., Chen Z., Cheong H., Cheong J.K., Chernyak B.V., Cherry S., Cheung C.F.R., Cheung C.H.A., Cheung K.-H., Chevet E., Chi R.J., Chiang A.K.S., Chiaradonna F., Chiarelli R., Chiariello M., Chica N., Chiocca S., 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[Ovid has truncated this field to avoid Excel character limitations], Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., 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Viret C., Viscomi M.T., Visnjic D., Vitale I., Vocadlo D.J., Voitsekhovskaja O.V., Volonte C., Volta M., Vomero M., Von Haefen C., Vooijs M.A., Voos W., Vucicevic L., Wade-Martins R., Waguri S., Waite K.A., and Wakatsuki S.
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.
- Published
- 2021
12. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
- Author
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[Ovid has truncated this field to avoid Excel character limitations], Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., 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Rogov V.V., Rojo A.I., Rolka K., Romanello V., Romani L., Romano A., Romano P.S., Romeo-Guitart D., Romero L.C., Romero M., Roney J.C., Rongo C., Roperto S., Rosenfeldt M.T., Rosenstiel P., Rosenwald A.G., Roth K.A., Roth L., Roth S., Rouschop K.M.A., Roussel B.D., Roux S., Rovere-Querini P., Roy A., Rozieres A., Ruano D., Rubinsztein D.C., Rubtsova M.P., Ruckdeschel K., Ruckenstuhl C., Rudolf E., Rudolf R., Ruggieri A., Ruparelia A.A., Rusmini P., Russell R.R., Russo G.L., Russo M., Russo R., Ryabaya O.O., Ryan K.M., Ryu K.-Y., Sabater-Arcis M., Sachdev U., Sacher M., Sachse C., Sadhu A., Sadoshima J., Safren N., Saftig P., Sagona A.P., Sahay G., Sahebkar A., Sahin M., Sahin O., Sahni S., Saito N., Saito S., Saito T., Sakai R., Sakai Y., Sakamaki J.-I., Saksela K., Salazar G., Salazar-Degracia A., Salekdeh G.H., Saluja A.K., Sampaio-Marques B., Sanchez M.C., Sanchez-Alcazar J.A., Sanchez-Vera V., Sancho-Shimizu V., Sanderson J.T., Sandri M., Santaguida S., Santambrogio L., Santana 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O., Vindis C., Viret C., Viscomi M.T., Visnjic D., Vitale I., Vocadlo D.J., Voitsekhovskaja O.V., Volonte C., Volta M., Vomero M., Von Haefen C., Vooijs M.A., Voos W., Vucicevic L., Wade-Martins R., Waguri S., Waite K.A., Wakatsuki S., Walker D.W., Walker M.J., Walker S.A., Walter J., Wandosell F.G., Wang B., Wang C., Wang C.-Y., Wang D., Wang F., Wang G., Wang H., Wang H.-G., Wang J., Wang K., Wang L., Wang M.H., Wang M., Wang N., Wang P., Wang Q.J., Wang Q., Wang Q.K., Wang Q.A., Wang W.-T., Wang W., Wang X., Wang Y.-Y., Wang Y., Wang Z., Warnes G., Warnsmann V., Watada H., Watanabe E., Watchon M., Wawrzynska A., Weaver T.E., Wegrzyn G., Wehman A.M., Wei H., Wei L., Wei T., Wei Y., Weiergraber O.H., Weihl C.C., Weindl G., Weiskirchen R., Wells A., Wen R.H., Wen X., Werner A., Weykopf B., Wheatley S.P., and W... [Ovid has truncated this field to avoid Excel character limitations]
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.
- Published
- 2021
13. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
- Author
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Gregory A, Taylor, Joan M, Tchetina, Elena, Tee, Andrew R, Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal A, Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei V, Testillano, Pilar S, Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind A, Thellung, Stefano, Thinwa, Josephine W, Thirumalaikumar, V P, Thomas, Sufi Mary, Thomes, Paul G, Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir I, Todi, Sokol V, Todorova, Krassimira, Toivonen, Janne M, Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon A, Torgersen, Maria L, Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina G, Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo H, Trelford, Charles B, Tremel, Shirley, Trougakos, Ioannis P, Tsao, Betty P, Tschan, Mario P, Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey S, Tumbarello, David A, Tumtas, Yasin, Tuñón, María J, Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley J, Tuxworth, Richard I, Tyler, Jessica K, Tyutereva, Elena V, Uchiyama, Yasuo, Ugun-Klusek, Aslihan, Uhlig, Holm H, Ułamek-Kozioł, Marzena, Ulasov, Ilya V, Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir N, Vaccari, Thomas, Vaccaro, Maria I, Vahsen, Björn F, Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria J, Valko, Ayelén, Vallee, Richard B, Valverde, Angela M, Van den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd J L, Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos A, Vannini, Nicola, Vanrell, M Cristina, Vantaggiato, Chiara, Varano, Gabriele, Varela-Nieto, Isabel, Varga, Máté, Vasconcelos, M Helena, Vats, Somya, Vavvas, Demetrios G, Vega-Naredo, Ignacio, Vega-Rubin-de-Celis, Silvia, Velasco, Guillermo, Velázquez, Ariadna P, Vellai, Tibor, Vellenga, Edo, Velotti, Francesca, Verdier, Mireille, Verginis, Panayotis, Vergne, Isabelle, Verkade, Paul, Verma, Manish, Verstreken, Patrik, Vervliet, Tim, Vervoorts, Jörg, Vessoni, Alexandre T, Victor, Victor M, Vidal, Michel, Vidoni, Chiara, Vieira, Otilia V, Vierstra, Richard D, Viganó, Sonia, Vihinen, Helena, Vijayan, Vinoy, Vila, Miquel, Vilar, Marçal, Villalba, José M, Villalobo, Antonio, Villarejo-Zori, Beatriz, Villarroya, Francesc, Villarroya, Joan, Vincent, Olivier, Vindis, Cecile, Viret, Christophe, Viscomi, Maria Teresa, Visnjic, Dora, Vitale, Ilio, Vocadlo, David J, Voitsekhovskaja, Olga V, Volonté, Cinzia, Volta, Mattia, Vomero, Marta, Von Haefen, Clarissa, Vooijs, Marc A, Voos, Wolfgang, Vucicevic, Ljubica, Wade-Martins, Richard, Waguri, Satoshi, Waite, Kenrick A, Wakatsuki, Shuji, Walker, David W, Walker, Mark J, Walker, Simon 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Alan, Wen, Runxia H, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally P, Whitton, J Lindsay, Whitworth, Alexander J, Wiktorska, Katarzyna, Wildenberg, Manon E, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin S B, Williams, Roger L, Williamson, Peter R, Wilson, Richard A, Winner, Beate, Winsor, Nathaniel J, Witkin, Steven S, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard W, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth K, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William K K, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik J, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-Tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, JinRong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna M S, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul M, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin K, Yiu, Stephanie Pei Tung, Yoo, Young H, Yoshida, Kiyotsugu, Yoshii, Saori R, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor C, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou F, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond L, Zacks, David N, Zaffagnini, Gabriele, Zambelli, Vanessa O, Zanella, Isabella, Zang, Qun S, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos S, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott O, Zeng, Jialiu, Zeng, Ju-Deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna D, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin Y B, Zhang, Leshuai W, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, Zhou, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-Jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine M, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry B, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith C, Stallings, Christina L, and Tong, Chun-Kit
- Abstract
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
- Published
- 2021
14. TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy
- Author
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Spitali, P., Zaharieva, I., Bohringer, S., Hiller, M., Chaouch, A., Roos, A., Scotton, C., Claustres, M., Bello, L., McDonald, C.M., Hoffman, E.P., Koeks, Z., Suchiman, H.E., Cirak, S., Scoto, M., Reza, M., Hoen, P.A.C. t, Niks, E.H., Tuffery-Giraud, S., Lochmuller, H., Ferlini, A., Muntoni, F., Aartsma-Rus, A., Dubrovsky, A., Kornberg, A., North, K., Ryan, M., Webster, R., Biggar, W.D., McAdam, L.C., Mah, J.K., Kolski, H., Vishwanathan, V., Chidambaranathan, S., Nevo, Y., Gorni, K., Carlo, J., Tulinius, M., Lotze, T., Bertorini, T.E., Day, J.W., Karachunski, P., Clemens, P.R., Abdel-Hamid, H., Teasley, J., Kuntz, N., Driscoll, S., Bodensteiner, J.B., Connolly, A.M., Pestronk, A., Abresch, R.T., Henricson, E.K., Joyce, N.C., Cnaan, A., Gordish-Dressmsn, H., Morgenroth, L.P., Leshner, R., Tesi-Rocha, C., Thangarajh, M., Duong, T., CINRG Investigators, Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universita degli Studi di Padova, Newcastle University [Newcastle], Department of Reproduction and Growth, UOL of Medical Genetics (University Hospital St Anna, Ferrara), University of Ferrara at St. Anna Hospital, Dubowitz Neuromuscular Center, Institute of Child Health, and Human Genetics
- Subjects
Male ,0301 basic medicine ,Adolescent ,Duchenne muscular dystrophy ,[SDV]Life Sciences [q-bio] ,Locus (genetics) ,Polymorphism, Single Nucleotide ,Genome-wide association studies ,Article ,Prognostic markers ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Genotype ,Genetics ,medicine ,Humans ,Allele ,Muscular dystrophy ,Child ,Genetics (clinical) ,Genes, Modifier ,biology ,business.industry ,Neuromuscular disease ,medicine.disease ,Muscular Dystrophy, Duchenne ,Phenotype ,030104 developmental biology ,Disease Progression ,biology.protein ,Human genome ,Dystrophin ,business ,030217 neurology & neurosurgery - Abstract
Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene leading to the lack of dystrophin. Variability in the disease course suggests that other factors influence disease progression. With this study we aimed to identify genetic factors that may account for some of the variability in the clinical presentation. We compared whole-exome sequencing (WES) data in 27 DMD patients with extreme phenotypes to identify candidate variants that could affect disease progression. Validation of the candidate SNPs was performed in two independent cohorts including 301 (BIO-NMD cohort) and 109 (CINRG cohort of European ancestry) DMD patients, respectively. Variants in the Tctex1 domain containing 1 (TCTEX1D1) gene on chromosome 1 were associated with age of ambulation loss. The minor alleles of two independent variants, known to affect TCTEX1D1 coding sequence and induce skipping of its exon 4, were associated with earlier loss of ambulation. Our data show that disease progression of DMD is affected by a new locus on chromosome 1 and demonstrate the possibility to identify genetic modifiers in rare diseases by studying WES data in patients with extreme phenotypes followed by multiple layers of validation.
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- 2020
15. TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy
- Author
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Spitali, P, Zaharieva, I, Bohringer, S, Hiller, M, Chaouch, A, Roos, A, Scotton, C, Claustres, M, Bello, L, McDonald, CM, Hoffman, EP, Koeks, Z, Suchiman, HE, Cirak, S, Scoto, M, Reza, M, 't Hoen, PAC, Niks, EH, Tuffery-Giraud, S, Lochmueller, H, Ferlini, A, Muntoni, F, Aartsma-Rus, A, Dubrovsky, A, Kornberg, A, North, K, Ryan, M, Webster, R, Biggar, WD, McAdam, LC, Mah, JK, Kolski, H, Vishwanathan, V, Chidambaranathan, S, Nevo, Y, Gorni, K, Carlo, J, Tulinius, M, Lotze, T, Bertorini, TE, Day, JW, Karachunski, P, Clemens, PR, Abdel-Hamid, H, Teasley, J, Kuntz, N, Driscoll, S, Bodensteiner, JB, Connolly, AM, Pestronk, A, Abresch, RT, Henricson, EK, Joyce, NC, Cnaan, A, Gordish-Dressmsn, H, Morgenroth, LP, Leshner, R, Tesi-Rocha, C, Thangarajh, M, Duong, T, Spitali, P, Zaharieva, I, Bohringer, S, Hiller, M, Chaouch, A, Roos, A, Scotton, C, Claustres, M, Bello, L, McDonald, CM, Hoffman, EP, Koeks, Z, Suchiman, HE, Cirak, S, Scoto, M, Reza, M, 't Hoen, PAC, Niks, EH, Tuffery-Giraud, S, Lochmueller, H, Ferlini, A, Muntoni, F, Aartsma-Rus, A, Dubrovsky, A, Kornberg, A, North, K, Ryan, M, Webster, R, Biggar, WD, McAdam, LC, Mah, JK, Kolski, H, Vishwanathan, V, Chidambaranathan, S, Nevo, Y, Gorni, K, Carlo, J, Tulinius, M, Lotze, T, Bertorini, TE, Day, JW, Karachunski, P, Clemens, PR, Abdel-Hamid, H, Teasley, J, Kuntz, N, Driscoll, S, Bodensteiner, JB, Connolly, AM, Pestronk, A, Abresch, RT, Henricson, EK, Joyce, NC, Cnaan, A, Gordish-Dressmsn, H, Morgenroth, LP, Leshner, R, Tesi-Rocha, C, Thangarajh, M, and Duong, T
- Abstract
Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene leading to the lack of dystrophin. Variability in the disease course suggests that other factors influence disease progression. With this study we aimed to identify genetic factors that may account for some of the variability in the clinical presentation. We compared whole-exome sequencing (WES) data in 27 DMD patients with extreme phenotypes to identify candidate variants that could affect disease progression. Validation of the candidate SNPs was performed in two independent cohorts including 301 (BIO-NMD cohort) and 109 (CINRG cohort of European ancestry) DMD patients, respectively. Variants in the Tctex1 domain containing 1 (TCTEX1D1) gene on chromosome 1 were associated with age of ambulation loss. The minor alleles of two independent variants, known to affect TCTEX1D1 coding sequence and induce skipping of its exon 4, were associated with earlier loss of ambulation. Our data show that disease progression of DMD is affected by a new locus on chromosome 1 and demonstrate the possibility to identify genetic modifiers in rare diseases by studying WES data in patients with extreme phenotypes followed by multiple layers of validation.
- Published
- 2020
16. The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy
- Author
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Thangarajh, M, Elfring, GL, Trifillis, P, McIntosh, J, Peitz, SW, Ryan, MM, Kornberg, AJ, RodriguezCasero, V, Wray, A, Jones, KJ, North, K, Goemans, N, Buyse, GM, Campbell, C, Mah, J, Sarnat, H, Selby, K, Voit, T, Doppler, V, De Castro, D, Chabrol, B, Levy, N, Halbert, C, Pereon, Y, Magot, A, Perrier, J, Mahe, JY, Schara, U, Lutz, S, Busse, M, Della Marina, A, Kirschner, J, Stanescu, A, Pohl, A, RensingZimmerman, C, Bertini, E, D'Amico, A, Kofler, A, Carlesi, A, Bonetti, AM, Santecchia, L, Emma, F, Bergami, G, Mercuri, EM, Vasco, G, Bianco, F, Mazzone, ES, De Sanctis, R, Alfieri, P, Pane, M, Messina, S, Comi, GP, Magri, F, Lucchini, V, Corti, SP, Moggio, MG, Sciacco, M, Bresolin, N, Prelle, AC, Magri, R, Virgilio, R, Lamperti, C, Nevo, Y, DorWollman, T, Vilchez, J, Muelas, N, Sevilla, T, Smeyers, P, de la Osa, A, Colomer, J, Ortez, CI, Nascimento, A, Febrer, A, Medina, J, Tulinus, M, Thorarinsdottir, B, Darin, N, Sejersen, T, Hovmoller, M, Bushby, K, Straub, V, Guglieri, M, Sarkozy, A, Willis, T, Eagle, M, Mayhew, A, Muntoni, F, Cirak, S, Manzur, AY, Robb, SA, Kinali, M, Quinlivan, RCM, Smith, MR, Pandey, R, Wong, B, Collins, J, Finkel, R, Bonnemann, C, Yang, M, Foley, AR, Yum, S, Sampson, J, Bromberg, M, Swoboda, K, Day, J, Karachunski, P, Mathews, K, Bonthius, D, Laubenthal, KS, Darras, B, Kang, P, Parson, J, Barohn, R, Dasouki, M, Anderson, H, Burns, J, Dimachkie, M, Pasnoor, M, Wang, YX, Ciafaloni, E, Heatwole, C, Connolly, A, Pestronk, A, Al-Lozi, M, Lopate, G, Golumbek, P, Sommerville, B, Wang, L, Wojcicka-Mitchell, A, Godbey, A, Harms, M, Varadachary, A, Iyadurai, S, Rojas, L, Iannacone, S, Khonghatithum, C, Sproule, D, De Vivo, D, Constantinescu, A, McDonald, C, Han, J, Ben Renfroe, Russman, B, Sussman, M, BurnsWechsler, S, Juel, V, Hobson-Webb, L, Smith, E, Ataluren Phase 2b Study Grp, Schara, Ulrike (Beitragende*r), and Marina, Adela Della (Beitragende*r)
- Subjects
Male ,0301 basic medicine ,Adolescent ,Duchenne muscular dystrophy ,Nonsense mutation ,Medizin ,Neuropsychological Tests ,030105 genetics & heredity ,Article ,Young Adult ,03 medical and health sciences ,Exon ,Settore MED/39 - NEUROPSICHIATRIA INFANTILE ,0302 clinical medicine ,Genotype ,Memory span ,medicine ,Humans ,Child ,Genetics ,biology ,Promoter ,Duchenne ,medicine.disease ,Muscular Dystrophy, Duchenne ,Cross-Sectional Studies ,Memory, Short-Term ,Codon, Nonsense ,Child, Preschool ,Mutation (genetic algorithm) ,biology.protein ,Neurology (clinical) ,Dystrophin ,030217 neurology & neurosurgery - Abstract
ObjectiveTo evaluate the relationship between deficit in digit span and genotype in nonsense mutation (nm) Duchenne muscular dystrophy (DMD) (nmDMD).MethodsWe investigated the relationship between normalized digit-span forward (d-sf) and digit-span backward (d-sb) scores to the location of nmDMD mutations in 169 participants ≥5 to ≤20 years who participated in a phase 2b clinical trial. Because alternative promoters are found upstream of DMD exons 30, 45, and 63, we correlated d-sf and d-sb to the specific nmDMD mutation location.ResultsParticipants with nm downstream of exon 30, downstream of exon 45, and downstream of exon 63 had significantly lower normalized d-sf scores (p < 0.0001). Participants with nm downstream of exon 45 in addition had significantly lower normalized d-sb score (p < 0.04). There was no significant difference in the normalized d-sb score in participants with mutations upstream or downstream of DMD exon 30 or upstream or downstream of DMD exon 63.ConclusionOur data provide evidence that specific cognitive deficits correlate to genotype in individuals with nmDMD, highlighting the critical role of brain-specific dystrophin isoforms in the neurobiological manifestations of this disease.Clinicaltrials.gov identifierNCT02090959.
- Published
- 2018
17. NDUFA4 MUTATIONS CAUSE MITOCHONDRIAL CYTOCHROME C OXIDASE DEFICIENCY LINKED TO HUMAN NEUROLOGICAL DISEASE: 33
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Pitceathly, R. D. S., Rahman, S., Wedatilake, Y., Polke, J. M., Cirak, S., Sailer, A., Foley, A. R., Hurles, M. E., Stalker, J., Hargreaves, I., Woodward, C. E., Sweeney, M. G., Muntoni, F., Houlden, H., Taanman, J-W, and Hanna, M. G.
- Published
- 2013
18. Emotional impact of genetic trials in progressive paediatric disorders: a dose-ranging exon-skipping trial in Duchenne muscular dystrophy
- Author
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Garralda, M. E., McConachie, H., Le Couteur, A., Sriranjan, S., Chakrabarti, I., Cirak, S., Guglieri, M., Bushby, K., and Muntoni, F.
- Published
- 2013
- Full Text
- View/download PDF
19. An unusual rod-core myopathy with distal weakness: a case report: O13
- Author
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Sewry, C. A., Feng, L., Scoto, M., Cirak, S., Jacques, T. S., Cullup, T., Abbs, S., Manzur, A., and Muntoni, F.
- Published
- 2012
20. Systemic administration of AVI-4658, a phosphorodiamidate morpholino oligomer to induce exon 51 skipping, is well tolerated and restores dystrophin expression in male children with Duchenne muscular dystrophy in a dose-dependent manner
- Author
-
CIRAK, S, ARECHAVALA-GOMEZA, V, GUGLIERI, M, FENG, L, TORELLI, S, ANTHONY, K, STRAUB, V, SHREWSBURY, S, SEWRY, C, MORGAN, J E, BUSHBY, K, and MUNTONI, F
- Published
- 2011
- Full Text
- View/download PDF
21. Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking
- Author
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Sprute, R, Bayram, N, Zeighami, J, Shariati, G, Azizi, Malamiri, Stumpfe, K, Mazaheri, N, Nedic, I, Efthymiou, S, Pergande, M, Cooper, E, Ozdemir, O, Kaçar, Bayram, Wang, H, Per, HÜSEYİN, Cirak, S, Jamshidi, Y, Shalbafan, B, Galehdari, H, Houlden, H, Salpietro, V, Sultan, T, Bibi, F, Sami, Güven, Yaşar, M, Tajik, M, and Naghibzadeh, SK
- Published
- 2019
22. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume
- Author
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Haworth, S, Shapland, CY, Hayward, C, Prins, BP, Felix, JF, Medina-Gomez, C, Rivadeneira, F, Wang, C, Ahluwalia, TS, Vrijheid, M, Guxens, M, Sunyer, J, Tachmazidou, I, Walter, K, Iotchkova, V, Jackson, A, Cleal, L, Huffmann, J, Min, JL, Sass, L, Timmers, PRHJ, Al Turki, S, Anderson, CA, Anney, R, Antony, D, Artigas, MS, Ayub, M, Bala, S, Barrett, JC, Barroso, I, Beales, P, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, DA, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Danecek, P, Day, INM, Day-Williams, A, Dominiczak, A, Down, T, Du, Y, Dunham, I, Durbin, R, Edkins, S, Ekong, R, Ellis, P, Evans, DM, Farooqi, IS, Fitzpatrick, DR, Flicek, P, Floyd, J, Foley, AR, Franklin, CS, Futema, M, Gallagher, L, Gaunt, TR, Geihs, M, Geschwind, D, Greenwood, CMT, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, AE, Holmans, P, Howie, B, Huang, J, Huang, L, Hubbard, T, Humphries, SE, Hurles, ME, Hysi, P, Jackson, DK, Jamshidi, Y, Joyce, C, Karczewski, KJ, Kaye, J, Keane, T, Kemp, JP, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, van Kogelenberg, M, Kolb-Kokocinski, A, Lachance, G, Langford, C, Lawson, D, Lee, I, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M, MacArthur, DG, Mangino, M, Marchini, J, Marenne, G, Maslen, J, Mathieson, I, McCarthy, S, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Memari, Y, Metrustry, S, Migone, N, Mitchison, HM, Moayyeri, A, Morris, A, Morris, J, Muddyman, D, Muntoni, F, Northstone, K, O'Donovan, MC, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, MJ, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, JR, Paternoster, L, Paunio, T, Payne, F, Payne, SJ, Perry, JRB, Pietilainen, O, Plagnol, V, Pollitt, RC, Porteous, DJ, Povey, S, Quail, MA, Quaye, L, Raymond, FL, Rehnstrom, K, Richards, JB, Ridout, CK, Ring, S, Ritchie, GRS, Roberts, N, Robinson, RL, Savage, DB, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, RH, Semple, RK, Serra, E, Sharp, SI, Shaw, A, Shihab, HA, Shin, S-Y, Skuse, D, Small, KS, Smee, C, Smith, BH, Soranzo, N, Southam, L, Spasic-Boskovic, O, Spector, TD, St Clair, D, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Taylor, R, Tian, J, Tobin, MD, Valdes, AM, Vandersteen, AM, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whyte, T, Williams, HJ, Williamson, KA, Wilson, C, Wilson, SG, Wong, K, Xu, C, Yang, J, Zhang, F, Zhang, P, Zheng, H-F, Smith, GD, Fisher, SE, Wilson, JF, Cole, TJ, Fernandez-Orth, D, Bonnelykke, K, Bisgaard, H, Pennell, CE, Jaddoe, VWV, Dedoussis, G, Timpson, N, Zeggini, E, Vitart, V, St Pourcain, B, UK10K Consortium, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, and Child and Adolescent Psychiatry / Psychology
- Abstract
Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.
- Published
- 2019
23. Kongenitale myasthene Syndrome im Erwachsenenalter
- Author
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Wunderlich, G., Abicht, A., Brunn, A., Daimagüler, H.-S., Schroeter, M., Fink, G. R., Lehmann, H. C., and Cirak, S.
- Subjects
ddc:610 - Abstract
Kongenitale myasthene Syndrome (CMS) stellen eine heterogene Gruppe von Erkrankungen dar, die mit einem breiten Spektrum von Phänotypen einhergehen, aber alle auf vererbte Defekte an der motorischen Endplatte zurückzuführen sind. Auch wenn einige Patienten bisher (noch) nicht genetisch charakterisiert werden können, hat die zunehmende Identifizierung ursächlicher Gene in den letzten Jahren neue Einblicke in die Funktionalität von Strukturproteinen der neuromuskulären Endplatte ermöglicht. Die Erstmanifestation der meisten CMS geschieht im Neugeborenen- bzw. Kleinkindesalter. Im Falle einer späteren Manifestation, oder wenn die Diagnose (z. B. aufgrund einer atypischen Manifestation) im Kleinkindesalter nicht gestellt wurde, ist die Diagnosestellung im Erwachsenenalter oft schwierig. Die Definition der zugrunde liegenden Mutation hat jedoch unmittelbare Therapierelevanz. In dieser Übersicht sollen ausgehend von charakteristischen Patientenbeispielen wesentliche klinische und zusatzdiagnostische Befunde verschiedener CMS-Subtypen dargestellt werden. Es wird insbesondere auch auf die differenzialdiagnostische Abgrenzung des CMS-Erkrankungsspektrums von Muskelerkrankungen im engeren Sinn, insbesondere von Muskeldystrophien, eingegangen. Zur Veranschaulichung geschieht dies einerseits mithilfe charakteristischer Patientenbeispiele und andererseits der Darstellung der wesentlichen klinischen und zusatzdiagnostischen Befunde verschiedener CMS-Subtypen sowie spezieller diagnostischer Hinweise.
- Published
- 2019
24. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume
- Author
-
Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), Pourcain, B.S. (Beate), Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), and Pourcain, B.S. (Beate)
- Abstract
Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for lowfrequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carrie
- Published
- 2019
- Full Text
- View/download PDF
25. Congenitalmyasthenic syndromes in adulthood. Challenging, rare but treatable
- Author
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Wunderlich, G., Abicht, A., Brunn, A., Daimagueler, H. -S., Schroeter, M., Fink, G. R., Lehmann, H. C., Cirak, S., Wunderlich, G., Abicht, A., Brunn, A., Daimagueler, H. -S., Schroeter, M., Fink, G. R., Lehmann, H. C., and Cirak, S.
- Abstract
The congenital myasthenic syndromes (CMS) represent aheterogeneous group of diseases with abroad spectrum of phenotypes. The common characteristic is an inherited genetic defect of the neuromuscular junction. Although in some patients the specific gene defect remains to be detected, the increasing identification of causative genes in recent years has already provided unique insights into the functionality of structural proteins at the neuromuscular junction. Neonatal and early childhood onset is observed in most CMS subtypes; however, late onset in adolescence or adulthood also occurs and establishing the diagnosis at these stages imposes particular challenges. To enable appropriate therapeutic interventions for an at least in principle treatable condition, determining the genetic cause is warranted. In this overview, the critical clinical and diagnostic features of the different CMS subtypes are presented and illustrated using typical cases. Furthermore, specific diagnostic clues are outlined. Finally, the overlap between CMS and muscular dystrophies is discussed. Illustrating characteristic patient examples, the essential clinical and additional diagnostic findings of various CMS subtypes and special diagnostic indications are presented.
- Published
- 2019
26. P.234Disruptive recessive TTN missense mutations cause a wide range of clinico-pathological features
- Author
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Rees, M., primary, Fukuzawa, A., additional, Nikoopour, R., additional, Kho, A., additional, Qi, J., additional, Fernandez-Garcia, M., additional, Wraige, E., additional, Cirak, S., additional, Pfuhl, M., additional, Fluss, J., additional, Muntoni, F., additional, Sarkozy, A., additional, Schröder, R., additional, Voermans, N., additional, Wilichowski, E., additional, Matthews, E., additional, Oates, E., additional, Ferreiro, A., additional, Jungbluth, H., additional, and Gautel, M., additional
- Published
- 2019
- Full Text
- View/download PDF
27. FV 49 Fast-myosin myopathy as a rare cause of external ophthalmoplegia and severe myopathy with tetraparesis
- Author
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Wunderlich, G., primary, Weis, J., additional, Kreutzer, M., additional, Abicht, A., additional, Vorgerd, M., additional, Fink, G.R., additional, Lehmann, H.C., additional, and Cirak, S., additional
- Published
- 2019
- Full Text
- View/download PDF
28. MYH2-assoziierte Myosin-Myopathie – seltene Ursache einer externen Ophthalmoplegie mit Tetraparese
- Author
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Wunderlich, G, additional, Weis, J, additional, Kreutzer, M, additional, Abicht, A, additional, Vorgerd, M, additional, Fink, GR, additional, Lehmann, HC, additional, and Cirak, S, additional
- Published
- 2019
- Full Text
- View/download PDF
29. Die genomische Ätiologie fetaler Akinesie
- Author
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Pergande, M, additional, Montameny, S, additional, Kawalia, A, additional, Daimagüler, H, additional, Becker, K, additional, Karakaya, M, additional, Elcioglu, N, additional, Ostojic, S, additional, Duman, î, additional, Koy, A, additional, Chao, CM, additional, Schoner, K, additional, Haliloglu, G, additional, Topaloglu, H, additional, Wang, H, additional, Kreutzer, M, additional, Thiele, H, additional, Altmüller, J, additional, Nürnberg, P, additional, Heller, R, additional, and Cirak, S, additional
- Published
- 2019
- Full Text
- View/download PDF
30. A scientific approach to improve Morpholino-based Exon-Skipping therapy for Duchenne Muscular Dystrophy
- Author
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Cirak, S, additional, Wang, H, additional, Novak, J, additional, Partridge, TA, additional, and Akpulat, U, additional
- Published
- 2019
- Full Text
- View/download PDF
31. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity
- Author
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Hendricks, AE, Bochukova, EG, Marenne, G, Keogh, JM, Atanassova, N, Bounds, R, Wheeler, E, Mistry, V, Henning, E, Körner, A, Muddyman, D, McCarthy, S, Hinney, A, Hebebrand, J, Scott, RA, Langenberg, C, Wareham, NJ, Surendran, P, Howson, JM, Butterworth, AS, Danesh, J, Nordestgaard, BG, Nielsen, SF, Afzal, S, Papadia, S, Ashford, S, Garg, S, Millhauser, GL, Palomino, RI, Kwasniewska, A, Tachmazidou, I, O'Rahilly, S, Zeggini, E, Barroso, I, Farooqi, IS, Benzeval, M, Burton, J, Buck, N, Jäckle, A, Kumari, M, Laurie, H, Lynn, P, Pudney, S, Rabe, B, Wolke, D, Overvad, K, Tjønneland, A, Clavel-Chapelon, F, Kaaks, R, Boeing, H, Trichopoulou, A, Ferrari, P, Palli, D, Krogha, V, Panico, S, Tuminoa, R, Matullo, G, Boer, J, Van Der Schouw, Y, Weiderpass, E, Quiros, JR, Sánchez, MJ, Navarro, C, Moreno-Iribas, C, Arriola, L, Melander, O, Wennberg, P, Key, TJ, Riboli, E, Turki, SA, Anderson, CA, Anney, R, Antony, D, Soler Artigas, M, Ayub, M, Bala, S, Barrett, JC, Beales, P, Bentham, J, Bhattacharyaa, S, Birney, E, Blackwooda, D, Bobrow, M, Bolton, PF, Boustred, C, Breen, G, Calissanoa, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampia, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Coccaa, M, Collier, DA, Cosgrove, C, Coxa, T, and Crooks, Lucy
- Abstract
© 2017 The Author(s). Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.
- Published
- 2017
32. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity
- Author
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Hendricks, A.E. Bochukova, E.G. Marenne, G. Keogh, J.M. Atanassova, N. Bounds, R. Wheeler, E. Mistry, V. Henning, E. Körner, A. Muddyman, D. McCarthy, S. Hinney, A. Hebebrand, J. Scott, R.A. Langenberg, C. Wareham, N.J. Surendran, P. Howson, J.M. Butterworth, A.S. Danesh, J. Nordestgaard, Bø.G. Nielsen, S.F. Afzal, S. Papadia, S. Ashford, S. Garg, S. Millhauser, G.L. Palomino, R.I. Kwasniewska, A. Tachmazidou, I. O'Rahilly, S. Zeggini, E. Barroso, I. Farooqi, I.S. Benzeval, M. Burton, J. Buck, N. Jäckle, A. Kumari, M. Laurie, H. Lynn, P. Pudney, S. Rabe, B. Wolke, D. Overvad, K. Tjønneland, A. Clavel-Chapelon, F. Kaaks, R. Boeing, H. Trichopoulou, A. Ferrari, P. Palli, D. Krogha, V. Panico, S. Tuminoa, R. Matullo, G. Boer, J. Van Der Schouw, Y. Weiderpass, E. Quiros, J.R. Sánchez, M.-J. Navarro, C. Moreno-Iribas, C. Arriola, L. Melander, O. Wennberg, P. Key, T.J. Riboli, E. Turki, S.A. Anderson, C.A. Anney, R. Antony, D. Soler Artigas, M. Ayub, M. Bala, S. Barrett, J.C. Beales, P. Bentham, J. Bhattacharyaa, S. Birney, E. Blackwooda, D. Bobrow, M. Bolton, P.F. Boustred, C. Breen, G. Calissanoa, M. Carss, K. Charlton, R. Chatterjee, K. Chen, L. Ciampia, A. Cirak, S. Clapham, P. Clement, G. Coates, G. Coccaa, M. Collier, D.A. Cosgrove, C. Coxa, T. Craddock, N. Crooks, L. Curran, S. Curtis, D. Daly, A. Danecek, P. Day, I.N.M. Day-Williams, A. Dominiczak, A. Down, T. Du, Y. Dunham, I. Durbin, R. Edkins, S. Ekong, R. Ellis, P. Evansa, D.M. Fitzpatrick, D.R. Flicek, P. Floyd, J. Foley, A.R. Franklin, C.S. Futema, M. Gallagher, L. Gaunt, T.R. Geihs, M. Geschwind, D. Greenwood, C.M.T. Griffin, H. Grozeva, D. Guo, X. Guo, X. Gurling, H. Hart, D. Holmans, P. Howie, B. Huang, J. Huang, L. Hubbard, T. Humphries, S.E. Hurles, M.E. Hysi, P. Iotchkova, V. Jackson, D.K. Jamshidi, Y. Joyce, C. Karczewski, K.J. Kaye, J. Keane, T. Kemp, J.P. Kennedy, K. Kent, A. Khawaja, F. Van Kogelenberg, M. Kolb-Kokocinski, A. Lachance, G. Langford, C. Lawson, D. Lee, I. Lek, M. Li, R. Li, Y. Liang, J. Lin, H. Liu, R. Lönnqvist, J. Lopes, L.R. Lopes, M. MacArthur, D.G. Mangino, M. Marchini, J. Maslen, J. Mathieson, I. McGuffin, P. McIntosh, A.M. McKechanie, A.G. McQuillin, A. Memari, Y. Metrustry, S. Migone, N. Min, J.L. Mitchison, H.M. Moayyeri, A. Morris, A. Morris, J. Muntoni, F. Northstone, K. O'Donovan, M.C. Onoufriadis, A. Oualkacha, K. Owen, M.J. Palotie, A. Panoutsopoulou, K. Parker, V. Parr, J.R. Paternoster, L. Paunio, T. Payne, F. Payne, S.J. Perry, J.R.B. Pietilainen, O. Plagnol, V. Pollitt, R.C. Porteous, D.J. Povey, S. Quail, M.A. Quaye, L. Raymond, F.L. Rehnström, K. Richards, J.B. Ridout, C.K. Ring, S. Ritchie, G.R.S. Roberts, N. Robinson, R.L. Savage, D.B. Scambler, P. Schiffels, S. Schmidts, M. Schoenmakers, N. Scott, R.H. Semple, R.K. Serra, E. Sharp, S.I. Shaw, A. Shihab, H.A. Shin, S.-Y. Skuse, D. Small, K.S. Smee, C. Smith, B.H. Davey Smith, G. Soranzo, N. Southam, L. Spasic-Boskovic, O. Spector, T.D. St Clair, D. St Pourcain, B. Stalker, J. Stevens, E. Sun, J. Surdulescu, G. Suvisaari, J. Syrris, P. Taylor, R. Tian, J. Timpson, N.J. Tobin, M.D. Valdes, A.M. Vandersteen, A.M. Vijayarangakannan, P. Visscher, P.M. Wain, L.V. Walter, K. Walters, J.T.R. Wang, G. Wang, J. Wang, Y. Ward, K. Whyte, T. Williams, H.J. Williamson, K.A. Wilson, C. Wilson, S.G. Wong, K. Xu, C. Yang, J. Zhang, F. Zhang, P. Zheng, H.-F.
- Abstract
Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).
- Published
- 2017
33. Kongenitale myasthene Syndrome im Erwachsenenalter
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Wunderlich, G., primary, Abicht, A., additional, Brunn, A., additional, Daimagüler, H.-S., additional, Schroeter, M., additional, Fink, G. R., additional, Lehmann, H. C., additional, and Cirak, S., additional
- Published
- 2018
- Full Text
- View/download PDF
34. 220th ENMC workshop: Dystroglycan and the dystroglycanopathies Naarden, The Netherlands, 27-29 May 2016
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Brown, S.C., Winder, S.J., Bevan, N., Bevan, L., Bokhoven, H. van, Campbell, K., Cirak, S., Lefeber, D.J., et al., Brown, S.C., Winder, S.J., Bevan, N., Bevan, L., Bokhoven, H. van, Campbell, K., Cirak, S., Lefeber, D.J., and et al.
- Abstract
Item does not contain fulltext
- Published
- 2017
35. Recessively-acting choline transporter mutations associated with severe congenital myasthenia disrupt transporter surface trafficking in vitro and in vivo
- Author
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Wang, H., Salter, S., Refai, O., Hardy, H., Sejersen, T., Wright, J., Zimmerman, H., Weis, J., Schara, U., Russell, M., Abdul-Rahman, O., Chilton, J., Blakely, R., Baple, E., Crosby, A., Cirak, S., Wang, H., Salter, S., Refai, O., Hardy, H., Sejersen, T., Wright, J., Zimmerman, H., Weis, J., Schara, U., Russell, M., Abdul-Rahman, O., Chilton, J., Blakely, R., Baple, E., Crosby, A., and Cirak, S.
- Published
- 2017
36. Genetic Landscape of congenital myasthenic syndroms from Turkey: novel mutations and clinical insights
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Yis, U., Becker, K., Kurul, S., Uyanik, G., Bayram, E., Haliloglu, G., Polat, I., Ayanoglu, M., Okur, D., Tosun, A., Serdaroglu, G., Yilmaz, S., Topaloglu, H., Anlar, B., Cirak, S., Engel, A., Yis, U., Becker, K., Kurul, S., Uyanik, G., Bayram, E., Haliloglu, G., Polat, I., Ayanoglu, M., Okur, D., Tosun, A., Serdaroglu, G., Yilmaz, S., Topaloglu, H., Anlar, B., Cirak, S., and Engel, A.
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- 2017
37. Translational biochemistry for dystroglycanopathies
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Wang, H., Sprute, R., Daimagueler, H., Cirak, S., Wang, H., Sprute, R., Daimagueler, H., and Cirak, S.
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- 2017
38. Severe form of recessive Charcot-Marie-Tooth disease with a novel mutation in myotubularin related protein 2
- Author
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Bayram, A., Stumpfe, K., Wang, H., Pergande, M., Per, H., Cirak, S., Bayram, A., Stumpfe, K., Wang, H., Pergande, M., Per, H., and Cirak, S.
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- 2017
39. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials (vol 134, pg 3547, 2011)
- Author
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Anthony, K., Cirak, S., Torelli, S., Tasca, G., Feng, L., Arechavala-Gomeza, V., Armaroli, A., Guglieri, M., Straathof, C.S., Verschuuren, J.J., Aartsma-Rus, A., Helderman-van den Enden, P., Bushby, K., Straub, V., Sewry, C., Ferlini, A., Ricci, E., Morgan, J.E., and Muntoni, F.
- Published
- 2016
40. Recessively-acting choline transporter mutations associated with severe congenital myasthenia disrupt transporter surface trafficking in vitro and in vivo
- Author
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Wang, H., primary, Salter, S., additional, Refai, O., additional, Hardy, H., additional, Sejersen, T., additional, Wright, J., additional, Zimmerman, H., additional, Weis, J., additional, Schara, U., additional, Russell, M., additional, Abdul-Rahman, O., additional, Chilton, J., additional, Blakely, R., additional, Baple, E., additional, Crosby, A., additional, and Cirak, S., additional
- Published
- 2017
- Full Text
- View/download PDF
41. Genetic Landscape of congenital myasthenic syndroms from Turkey: novel mutations and clinical insights
- Author
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Yiş, U., primary, Becker, K., additional, Kurul, S., additional, Uyanik, G., additional, Bayram, E., additional, Haliloglu, G., additional, Polat, I., additional, Ayanoglu, M., additional, Okur, D., additional, Tosun, A., additional, Serdaroglu, G., additional, Yılmaz, S., additional, Topaloğlu, H., additional, Anlar, B., additional, Cirak, S., additional, and Engel, A., additional
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- 2017
- Full Text
- View/download PDF
42. Translational biochemistry for dystroglycanopathies
- Author
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Wang, H., primary, Sprute, R., additional, Daimagüler, H., additional, and Cirak, S., additional
- Published
- 2017
- Full Text
- View/download PDF
43. P 42 Congenital myasthenia in adult patients – a diagnostic and therapeutic challenge
- Author
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Ritter, C., primary, Cirak, S., additional, Abicht, A., additional, Lehmann, H.C., additional, Brunn, A., additional, Fink, G., additional, Schroeter, M., additional, and Wunderlich, G., additional
- Published
- 2017
- Full Text
- View/download PDF
44. G.P.228 - Micro RNA profile associated with the dystrophin level in Becker muscular dystrophy
- Author
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Zaharieva, I, Cirak, S, Anthony, Karen, Feng, L, Tasca, G, Ferlini, A, Morgan, J, and Muntoni, F
- Subjects
musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,musculoskeletal system ,nervous system diseases - Abstract
Becker (BMD) and Duchenne muscular dystrophy (DMD) are allelic disorders arising from mutations in the dystrophin gene. In-frame mutations lead to the milder BMD while out-of-frame mutations disrupt the reading frame and lead to the severe DMD with lack of dystrophin. A therapeutic strategy for skipping specific exons in dystrophin and restoring the open reading frame has been successfully applied in DMD; this “converts” the out-of-frame deletion in DMD to BMD-like in-frame deletion. Micro RNAs (miRs) are small RNA sequences that regulate gene expression post-transcriptionally.
- Published
- 2015
45. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel
- Author
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Huang, J, Howie, B, Mccarthy, S, Memari, Y, Walter, K, Min, Jl, Danecek, P, Malerba, Giovanni, Trabetti, Elisabetta, Zheng, Hf, Gambaro, G, Richards, Jb, Durbin, R, Timpson, Nj, Marchini, J, Soranzo, N, Al Turki, S, Amuzu, A, Anderson, Ca, Anney, R, Antony, D, Artigas, Ms, Ayub, M, Bala, S, Barrett, Jc, Barroso, I, Beales, P, Benn, M, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, Pf, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Casas, Jp, Chambers, Jc, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, Da, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Day, In, Day Williams, A, Dedoussis, G, Down, T, Du, Y, van Duijn, Cm, Dunham, I, Edkins, S, Ekong, R, Ellis, P, Evans, Dm, Farooqi, Is, Fitzpatrick, Dr, Flicek, P, Floyd, J, Foley, Ar, Franklin, Cs, Futema, M, Gallagher, L, Gasparini, P, Gaunt, Tr, Geihs, M, Geschwind, D, Greenwood, C, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, Ae, Holmans, P, Huang, L, Hubbard, T, Humphries, Se, Hurles, Me, Hysi, P, Iotchkova, V, Isaacs, A, Jackson, Dk, Jamshidi, Y, Johnson, J, Joyce, C, Karczewski, Kj, Kaye, J, Keane, T, Kemp, Jp, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, Kleber, Me, van Kogelenberg, M, Kolb Kokocinski, A, Kooner, Js, Lachance, G, Langenberg, C, Langford, C, Lawson, D, Lee, I, van Leeuwen, Em, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lönnqvist, J, Lopes, Lr, Lopes, M, Luan, J, Macarthur, Dg, Mangino, M, Marenne, G, März, W, Maslen, J, Matchan, A, Mathieson, I, Mcguffin, P, Mcintosh, Am, Mckechanie, Ag, Mcquillin, A, Metrustry, S, Migone, N, Mitchison, Hm, Moayyeri, A, Morris, J, Morris, R, Muddyman, D, Muntoni, F, Nordestgaard, Bg, Northstone, K, O'Donovan, Mc, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, Mj, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, Jr, Paternoster, L, Paunio, T, Payne, F, Payne, Sj, Perry, Jr, Pietilainen, O, Plagnol, V, Pollitt, Rc, Povey, S, Quail, Ma, Quaye, L, Raymond, L, Rehnström, K, Ridout, Ck, Ring, S, Ritchie, Gr, Roberts, N, Robinson, Rl, Savage, Db, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, Rh, Scott, Ra, Semple, Rk, Serra, E, Sharp, Si, Shaw, A, Shihab, Ha, Shin, Sy, Skuse, D, Small, Ks, Smee, C, Smith, Gd, Southam, L, Spasic Boskovic, O, Spector, Td, St Clair, D, St Pourcain, B, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Tachmazidou, I, Taylor, R, Tian, J, Tobin, Md, Toniolo, D, Traglia, M, Tybjaerg Hansen, A, Valdes, Am, Vandersteen, Am, Varbo, A, Vijayarangakannan, P, Visscher, Pm, Wain, Lv, Walters, Jt, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whincup, P, Whyte, T, Williams, Hj, Williamson, Ka, Wilson, C, Wilson, Sg, Wong, K, Xu, C, Yang, J, Zaza, Gianluigi, Zeggini, E, Zhang, F, Zhang, P, Zhang, W., Clinicum, Department of Psychiatry, Jie, Huang, Bryan, Howie, Shane, Mccarthy, Yasin, Memari, Klaudia, Walter, Josine L., Min, Petr, Danecek, Giovanni, Malerba, Elisabetta, Trabetti, Hou Feng, Zheng, Saeed Al, Turki, Antoinette, Amuzu, Carl A., Anderson, Richard, Anney, Dinu, Antony, María Soler, Artiga, Muhammad, Ayub, Senduran, Bala, Jeffrey C., Barrett, Inês, Barroso, Phil, Beale, Marianne, Benn, Jamie, Bentham, Shoumo, Bhattacharya, Ewan, Birney, Douglas, Blackwood, Martin, Bobrow, Elena, Bochukova, Patrick F., Bolton, Rebecca, Bound, Chris, Boustred, Gerome, Breen, Mattia, Calissano, Keren, Car, Juan Pablo, Casa, John C., Chamber, Ruth, Charlton, Krishna, Chatterjee, Lu, Chen, Antonio, Ciampi, Sebahattin, Cirak, Peter, Clapham, Gail, Clement, Guy, Coate, Cocca, Massimiliano, David A., Collier, Catherine, Cosgrove, Tony, Cox, Nick, Craddock, Lucy, Crook, Sarah, Curran, David, Curti, Allan, Daly, Ian N. M., Day, Aaron Day, William, George, Dedoussi, Thomas, Down, Yuanping, Du, Cornelia M., van Duijn, Ian, Dunham, Sarah, Edkin, Rosemary, Ekong, Peter, Elli, David M., Evan, I., Sadaf Farooqi, David R., Fitzpatrick, Paul, Flicek, James, Floyd, A., Reghan Foley, Christopher S., Franklin, Marta, Futema, Louise, Gallagher, Gasparini, Paolo, Tom R., Gaunt, Matthias, Geih, Daniel, Geschwind, Celia, Greenwood, Heather, Griffin, Detelina, Grozeva, Xiaosen, Guo, Xueqin, Guo, Hugh, Gurling, Deborah, Hart, Audrey E., Hendrick, Peter, Holman, Liren, Huang, Tim, Hubbard, Steve E., Humphrie, Matthew E., Hurle, Pirro, Hysi, Valentina, Iotchkova, Aaron, Isaac, David K., Jackson, Yalda, Jamshidi, Jon, Johnson, Chris, Joyce, Konrad J., Karczewski, Jane, Kaye, Thomas, Keane, John P., Kemp, Karen, Kennedy, Alastair, Kent, Julia, Keogh, Farrah, Khawaja, Marcus E., Kleber, Margriet van, Kogelenberg, Anja Kolb, Kokocinski, Jaspal S., Kooner, Genevieve, Lachance, Claudia, Langenberg, Cordelia, Langford, Daniel, Lawson, Irene, Lee, Elisabeth M., van Leeuwen, Monkol, Lek, Rui, Li, Yingrui, Li, Jieqin, Liang, Hong, Lin, Ryan, Liu, Jouko, Lönnqvist, Luis R., Lope, Margarida, Lope, Jian'An, Luan, Daniel G., Macarthur, Massimo, Mangino, Gaëlle, Marenne, Winfried, März, John, Maslen, Angela, Matchan, Iain, Mathieson, Peter, Mcguffin, Andrew M., Mcintosh, Andrew G., Mckechanie, Andrew, Mcquillin, Sarah, Metrustry, Nicola, Migone, Hannah M., Mitchison, Alireza, Moayyeri, James, Morri, Richard, Morri, Dawn, Muddyman, Francesco, Muntoni, Børge G., Nordestgaard, Kate, Northstone, Michael C., O'Donovan, Stephen, O'Rahilly, Alexandros, Onoufriadi, Karim, Oualkacha, Michael J., Owen, Aarno, Palotie, Kalliope, Panoutsopoulou, Victoria, Parker, Jeremy R., Parr, Lavinia, Paternoster, Tiina, Paunio, Felicity, Payne, Stewart J., Payne, John R. B., Perry, Olli, Pietilainen, Vincent, Plagnol, Rebecca C., Pollitt, Sue, Povey, Michael A., Quail, Lydia, Quaye, Lucy, Raymond, Karola, Rehnström, Cheryl K., Ridout, Susan, Ring, Graham R. S., Ritchie, Nicola, Robert, Rachel L., Robinson, David B., Savage, Peter, Scambler, Stephan, Schiffel, Miriam, Schmidt, Nadia, Schoenmaker, Richard H., Scott, Robert A., Scott, Robert K., Semple, Eva, Serra, Sally I., Sharp, Adam, Shaw, Hashem A., Shihab, So Youn, Shin, David, Skuse, Kerrin S., Small, Carol, Smee, George Davey, Smith, Lorraine, Southam, Olivera Spasic, Boskovic, Timothy D., Spector, David St, Clair, Beate St, Pourcain, Jim, Stalker, Elizabeth, Steven, Jianping, Sun, Gabriela, Surdulescu, Jaana, Suvisaari, Petros, Syrri, Ioanna, Tachmazidou, Rohan, Taylor, Jing, Tian, Martin D., Tobin, Daniela, Toniolo, Michela, Traglia, Anne Tybjaerg, Hansen, Ana M., Valde, Anthony M., Vandersteen, Anette, Varbo, Parthiban, Vijayarangakannan, Peter M., Visscher, Louise V., Wain, James T. R., Walter, Guangbiao, Wang, Jun, Wang, Yu, Wang, Kirsten, Ward, Eleanor, Wheeler, Peter, Whincup, Tamieka, Whyte, Hywel J., William, Kathleen A., Williamson, Crispian, Wilson, Scott G., Wilson, Kim, Wong, Changjiang, Xu, Jian, Yang, Gianluigi, Zaza, Eleftheria, Zeggini, Feng, Zhang, Pingbo, Zhang, Weihua, Zhang, Giovanni, Gambaro, J., Brent Richard, Richard, Durbin, Nicholas J., Timpson, Jonathan, Marchini, and Nicole, Soranzo
- Subjects
Computer science ,General Physics and Astronomy ,Genome-wide association study ,0302 clinical medicine ,Gene Frequency ,Haplotype ,Genetics,Biological sciences ,Settore MED/14 - NEFROLOGIA ,Aged, 80 and over ,Genetics ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,TWINSUK ,Middle Aged ,single-nucleotide polymorphism ,Whole-genome sequencing, WGS imputation panel, single-nucleotide polymorphism ,Biological sciences ,Italy ,MAP ,Adult ,Adolescent ,Genotype ,WGS imputation panel ,Population ,Single-nucleotide polymorphism ,FORMAT ,Computational biology ,GENOTYPE IMPUTATION ,Polymorphism, Single Nucleotide ,Article ,White People ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,Humans ,GENOME-WIDE ASSOCIATION ,1000 Genomes Project ,education ,Allele frequency ,Alleles ,Aged ,030304 developmental biology ,Whole-genome sequencing ,Models, Statistical ,Models, Genetic ,Genome, Human ,Genetic Variation ,General Chemistry ,United Kingdom ,Minor allele frequency ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Haplotypes ,3111 Biomedicine ,030217 neurology & neurosurgery ,Imputation (genetics) - Abstract
Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants., Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.
- Published
- 2015
46. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation
- Author
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Jansen, J.C., Cirak, S., Scherpenzeel, M. van, Timal, S., Reunert, J., Rust, S., Perez, B., Vicogne, D., Krawitz, P., Wada, Y., Ashikov, A.M., Perez-Cerda, C., Medrano, C., Arnoldy, A., Hoischen, A., Huijben, K., Steenbergen, G., Quelhas, D., Diogo, L., Rymen, D., Jaeken, J., Guffon, N., Cheillan, D., Heuvel, B. van den, Maeda, Y., Kaiser, O., Schara, U., Gerner, P., Boogert, M.A. van den, Holleboom, A.G., Nassogne, M.C., Sokal, E., Salomon, J., Bogaart, G. van den, Drenth, J.P., Huynen, M.A., Veltman, J.A., Wevers, R.A., Morava, E., Matthijs, G., Foulquier, F., Marquardt, T., Lefeber, D.J., Jansen, J.C., Cirak, S., Scherpenzeel, M. van, Timal, S., Reunert, J., Rust, S., Perez, B., Vicogne, D., Krawitz, P., Wada, Y., Ashikov, A.M., Perez-Cerda, C., Medrano, C., Arnoldy, A., Hoischen, A., Huijben, K., Steenbergen, G., Quelhas, D., Diogo, L., Rymen, D., Jaeken, J., Guffon, N., Cheillan, D., Heuvel, B. van den, Maeda, Y., Kaiser, O., Schara, U., Gerner, P., Boogert, M.A. van den, Holleboom, A.G., Nassogne, M.C., Sokal, E., Salomon, J., Bogaart, G. van den, Drenth, J.P., Huynen, M.A., Veltman, J.A., Wevers, R.A., Morava, E., Matthijs, G., Foulquier, F., Marquardt, T., and Lefeber, D.J.
- Abstract
Contains fulltext : 167630.pdf (publisher's version ) (Closed access), Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal glyc
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- 2016
47. GNE myopathy in Roma patients homozygous for the p.I618T founder mutation
- Author
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Chamova, T., Gospodinova, M., Guergueltcheva, V., Krause, S., Cirak, S., Kaprelyan, A., Angelova, L., Mihaylova, V., Bichev, S., Chandler, D., Naydenov, E., Grudkova, M., Djukmedzhiev, P., Bogdanova, D., Kmetska, K., Voit, T., Pogoryelova, O., Lochmuller, H., Goebel, H., Bahlo, M., Kalaydjieva, L., Tournev, I., Chamova, T., Gospodinova, M., Guergueltcheva, V., Krause, S., Cirak, S., Kaprelyan, A., Angelova, L., Mihaylova, V., Bichev, S., Chandler, D., Naydenov, E., Grudkova, M., Djukmedzhiev, P., Bogdanova, D., Kmetska, K., Voit, T., Pogoryelova, O., Lochmuller, H., Goebel, H., Bahlo, M., Kalaydjieva, L., and Tournev, I.
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- 2016
48. DMD genotypes and loss of ambulation in the CINRG Duchenne natural history study
- Author
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Bello, L., Morgenroth, L., Gordish-Dressman, H., Hoffman, E., McDonald, C., Cirak, S., Bello, L., Morgenroth, L., Gordish-Dressman, H., Hoffman, E., McDonald, C., and Cirak, S.
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- 2016
49. A new homozygous frameshifting mutation in SPEG causes mild centronuclear myopathy
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Bayram, A. Kacar, Per, H., Zorludemir, S., Wang, H., Gumus, H., Cirak, S., Bayram, A. Kacar, Per, H., Zorludemir, S., Wang, H., Gumus, H., and Cirak, S.
- Published
- 2016
50. Congenital mirror movements in alpha-dystroglycanopathy (ADG) due to SGK196 mutation
- Author
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Ardicli, D., Gocmen, R., Cirak, S., Talim, B., Haliloglu, G., Topaloglu, H., Ardicli, D., Gocmen, R., Cirak, S., Talim, B., Haliloglu, G., and Topaloglu, H.
- Published
- 2016
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