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274 results on '"Goldwurm, S."'

4. An exome study of Parkinsonʼs disease in Sardinia, a Mediterranean genetic isolate: 165

Author

Quadri, M., Yang, X., Cossu, G., Olgiati, S., Saddi, V., Breedveld, G. J., Ouyang, L., Hu, J., Xu, N., Graafland, J., Ricchi, V., Murgia, D., Guedes, Correia L., Mariani, C., Martí, M. J., Tarantino, P., Asselta, R., Valldeoriola, F., Gagliardi, M., Pezzoli, G., Ezquerra, M., Quattrone, A., Ferreira, J., Annesi, G., Goldwurm, S., Tolosa, E., Oostra, B. A., Melis, M., Wang, J., and Bonifati, V.

Published
2014

6. Using global team science to identify genetic parkinson's disease worldwide

Author

Vollstedt, E, Kasten, M, Klein, C, Aasly, J, Adler, C, Ahmad-Annuar, A, Albanese, A, Alcalay, R, Al-Mubarak, B, Alvarez, V, Andree-Munoz, B, Annesi, G, Appel-Cresswell, S, Arkadir, D, Armasu, S, Barber, T, Bardien, S, Barkhuizen, M, Barrett, M, Basak, A, Beach, T, Benitez, B, Berg, D, Bhatia, K, Binkofski, F, Blauwendraat, C, Bonifati, V, Borges, V, Bozi, M, Brice, A, Brighina, L, Brockmann, K, Brucke, T, Bruggemann, N, Camacho, M, Cardoso, F, Belin, A, Carr, J, Chan, P, Chang-Castello, J, Chase, B, Chen-Plotkin, A, Ju Chung, S, Cilia, R, Clarimon, J, Clark, L, Cornejo-Olivas, M, Corvol, J, Cosentino, C, Cras, P, Crosiers, D, Damasio, J, Das, P, de Carvalho Aguiar, P, De Michele, G, De Rosa, A, Dieguez, E, Dorszewska, J, Erer, S, Ertan, S, Farrer, M, Fedotova, E, Ferese, R, Ferrarese, C, Ferraz, H, Fiala, O, Foroud, T, Friedman, A, Frigerio, R, Funayama, M, Gambardella, S, Garraux, G, Gatto, E, Genc, G, Giladi, N, Goldwurm, S, Gomez-Esteban, J, Gomez-Garre, P, Gorostidi, A, Grosset, D, Hanagasi, H, Hardy, J, Hassan, A, Hattori, N, Hauser, R, Hedera, P, Hentati, F, Hertz, J, Holton, J, Houlden, H, Hutz, M, Ikeuchi, T, Illarioshkin, S, Inca-Martinez, M, Infante, J, Jankovic, J, Jeon, B, Jesus, S, Jimenez-Del-Rio, M, Kaasinen, V, Kataoka, H, Kawakami, H, Kim, Y, Klivenyi, P, Koks, S, Konig, I, Kostic, V, Koziorowski, D, Kruger, R, Krygowska-Wajs, A, Kulisevsky, J, Lai, D, Lang, A, Ledoux, M, Lesage, S, Lim, S, Lin, C, Lohmann, K, Lopera, F, Lopez, G, Lu, C, Lynch, T, Machaczka, M, Madoev, H, Magalhaes, M, Majamaa, K, Maraganore, D, Marder, K, Markopoulou, K, Martikainen, M, Mata, I, Mazzetti, P, Mellick, G, Menendez-Gonzalez, M, Micheli, F, Mirelman, A, Mir, P, Morino, H, Morris, H, Munhoz, R, Naito, A, Olszewska, D, Ozelius, L, Padmanabhan, S, Paisan-Ruiz, C, Payami, H, Peluso, S, Petkovic, S, Petrucci, S, Pezzoli, G, Pimentel, M, Pirker, W, Pramstaller, P, Pulkes, T, Puschmann, A, Quattrone, A, Raggio, V, Ransmayr, G, Rieder, C, Riess, O, Rodriguez-Porcel, F, Rogaeva, E, Ross, O, Ruiz-Martinez, J, Sammler, E, San Luciano, M, Satake, W, Saunders-Pullman, R, Sazci, A, Scherzer, C, Schrag, A, Schumacher-Schuh, A, Sharma, M, Sidransky, E, Singleton, A, Petersen, M, Smolders, S, Spitz, M, Stefanis, L, Struhal, W, Sue, C, Swan, M, Swanberg, M, Taba, P, Taipa, R, Tan, M, Tan, A, Tan, E, Tang, B, Tayebi, N, Thaler, A, Thomas, A, Toda, T, Toft, M, Torres, L, Tumas, V, Valente, E, Van Broeckhoven, C, Vecsei, L, Velez-Pardo, C, Vidailhet, M, Warner, T, Williams-Gray, C, Winkelmann, J, Woitalla, D, Wood, N, Wszolek, Z, Wu, R, Wu, Y, Xie, T, Yoshino, H, Zhang, B, Zimprich, A, Vollstedt E. -J., Kasten M., Klein C., Aasly J., Adler C., Ahmad-Annuar A., Albanese A., Alcalay R. N., Al-Mubarak B., Alvarez V., Andree-Munoz B., Annesi G., Appel-Cresswell S., Arkadir D., Armasu S., Barber T. R., Bardien S., Barkhuizen M., Barrett M. J., Basak A. N., Beach T., Benitez B. A., Berg D., Bhatia K., Binkofski F., Blauwendraat C., Bonifati V., Borges V., Bozi M., Brice A., Brighina L., Brockmann K., Brucke T., Bruggemann N., Camacho M., Cardoso F., Belin A. C., Carr J., Chan P., Chang-Castello J., Chase B., Chen-Plotkin A., Ju Chung S., Cilia R., Clarimon J., Clark L., Cornejo-Olivas M., Corvol J. -C., Cosentino C., Cras P., Crosiers D., Damasio J., Das P., de Carvalho Aguiar P., De Michele G., De Rosa A., Dieguez E., Dorszewska J., Erer S., Ertan S., Farrer M., Fedotova E., Ferese R., Ferrarese C., Ferraz H., Fiala O., Foroud T., Friedman A., Frigerio R., Funayama M., Gambardella S., Garraux G., Gatto E. M., Genc G., Giladi N., Goldwurm S., Gomez-Esteban J. C., Gomez-Garre P., Gorostidi A., Grosset D., Hanagasi H., Hardy J., Hassan A., Hattori N., Hauser R. A., Hedera P., Hentati F., Hertz J. M., Holton J. L., Houlden H., Hutz M. H., Ikeuchi T., Illarioshkin S., Inca-Martinez M., Infante J., Jankovic J., Jeon B. S., Jesus S., Jimenez-Del-Rio M., Kaasinen V., Kataoka H., Kawakami H., Kim Y. J., Klivenyi P., Koks S., Konig I. R., Kostic V., Koziorowski D., Kruger R., Krygowska-Wajs A., Kulisevsky J., Lai D., Lang A., LeDoux M., Lesage S., Lim S. -Y., Lin C. -H., Lohmann K., Lopera F., Lopez G., Lu C. -S., Lynch T., Machaczka M., Madoev H., Magalhaes M., Majamaa K., Maraganore D., Marder K., Markopoulou K., Martikainen M. H., Mata I., Mazzetti P., Mellick G., Menendez-Gonzalez M., Micheli F., Mirelman A., Mir P., Morino H., Morris H., Munhoz R. P., Naito A., Olszewska D. A., Ozelius L. J., Padmanabhan S., Paisan-Ruiz C., Payami H., Peluso S., Petkovic S., Petrucci S., Pezzoli G., Pimentel M., Pirker W., Pramstaller P. P., Pulkes T., Puschmann A., Quattrone A., Raggio V., Ransmayr G., Rieder C., Riess O., Rodriguez-Porcel F., Rogaeva E., Ross O. A., Ruiz-Martinez J., Sammler E., San Luciano M., Satake W., Saunders-Pullman R., Sazci A., Scherzer C., Schrag A., Schumacher-Schuh A., Sharma M., Sidransky E., Singleton A. B., Petersen M. S., Smolders S., Spitz M., Stefanis L., Struhal W., Sue C. M., Swan M., Swanberg M., Taba P., Taipa R., Tan M., Tan A. H., Tan E. -K., Tang B., Tayebi N., Thaler A., Thomas A., Toda T., Toft M., Torres L., Tumas V., Valente E. M., Van Broeckhoven C., Vecsei L., Velez-Pardo C., Vidailhet M., Warner T. T., Williams-Gray C. H., Winkelmann J., Woitalla D., Wood N. W., Wszolek Z. K., Wu R. -M., Wu Y. -R., Xie T., Yoshino H., Zhang B., Zimprich A., Vollstedt, E, Kasten, M, Klein, C, Aasly, J, Adler, C, Ahmad-Annuar, A, Albanese, A, Alcalay, R, Al-Mubarak, B, Alvarez, V, Andree-Munoz, B, Annesi, G, Appel-Cresswell, S, Arkadir, D, Armasu, S, Barber, T, Bardien, S, Barkhuizen, M, Barrett, M, Basak, A, Beach, T, Benitez, B, Berg, D, Bhatia, K, Binkofski, F, Blauwendraat, C, Bonifati, V, Borges, V, Bozi, M, Brice, A, Brighina, L, Brockmann, K, Brucke, T, Bruggemann, N, Camacho, M, Cardoso, F, Belin, A, Carr, J, Chan, P, Chang-Castello, J, Chase, B, Chen-Plotkin, A, Ju Chung, S, Cilia, R, Clarimon, J, Clark, L, Cornejo-Olivas, M, Corvol, J, Cosentino, C, Cras, P, Crosiers, D, Damasio, J, Das, P, de Carvalho Aguiar, P, De Michele, G, De Rosa, A, Dieguez, E, Dorszewska, J, Erer, S, Ertan, S, Farrer, M, Fedotova, E, Ferese, R, Ferrarese, C, Ferraz, H, Fiala, O, Foroud, T, Friedman, A, Frigerio, R, Funayama, M, Gambardella, S, Garraux, G, Gatto, E, Genc, G, Giladi, N, Goldwurm, S, Gomez-Esteban, J, Gomez-Garre, P, Gorostidi, A, Grosset, D, Hanagasi, H, Hardy, J, Hassan, A, Hattori, N, Hauser, R, Hedera, P, Hentati, F, Hertz, J, Holton, J, Houlden, H, Hutz, M, Ikeuchi, T, Illarioshkin, S, Inca-Martinez, M, Infante, J, Jankovic, J, Jeon, B, Jesus, S, Jimenez-Del-Rio, M, Kaasinen, V, Kataoka, H, Kawakami, H, Kim, Y, Klivenyi, P, Koks, S, Konig, I, Kostic, V, Koziorowski, D, Kruger, R, Krygowska-Wajs, A, Kulisevsky, J, Lai, D, Lang, A, Ledoux, M, Lesage, S, Lim, S, Lin, C, Lohmann, K, Lopera, F, Lopez, G, Lu, C, Lynch, T, Machaczka, M, Madoev, H, Magalhaes, M, Majamaa, K, Maraganore, D, Marder, K, Markopoulou, K, Martikainen, M, Mata, I, Mazzetti, P, Mellick, G, Menendez-Gonzalez, M, Micheli, F, Mirelman, A, Mir, P, Morino, H, Morris, H, Munhoz, R, Naito, A, Olszewska, D, Ozelius, L, Padmanabhan, S, Paisan-Ruiz, C, Payami, H, Peluso, S, Petkovic, S, Petrucci, S, Pezzoli, G, Pimentel, M, Pirker, W, Pramstaller, P, Pulkes, T, Puschmann, A, Quattrone, A, Raggio, V, Ransmayr, G, Rieder, C, Riess, O, Rodriguez-Porcel, F, Rogaeva, E, Ross, O, Ruiz-Martinez, J, Sammler, E, San Luciano, M, Satake, W, Saunders-Pullman, R, Sazci, A, Scherzer, C, Schrag, A, Schumacher-Schuh, A, Sharma, M, Sidransky, E, Singleton, A, Petersen, M, Smolders, S, Spitz, M, Stefanis, L, Struhal, W, Sue, C, Swan, M, Swanberg, M, Taba, P, Taipa, R, Tan, M, Tan, A, Tan, E, Tang, B, Tayebi, N, Thaler, A, Thomas, A, Toda, T, Toft, M, Torres, L, Tumas, V, Valente, E, Van Broeckhoven, C, Vecsei, L, Velez-Pardo, C, Vidailhet, M, Warner, T, Williams-Gray, C, Winkelmann, J, Woitalla, D, Wood, N, Wszolek, Z, Wu, R, Wu, Y, Xie, T, Yoshino, H, Zhang, B, Zimprich, A, Vollstedt E. -J., Kasten M., Klein C., Aasly J., Adler C., Ahmad-Annuar A., Albanese A., Alcalay R. N., Al-Mubarak B., Alvarez V., Andree-Munoz B., Annesi G., Appel-Cresswell S., Arkadir D., Armasu S., Barber T. R., Bardien S., Barkhuizen M., Barrett M. J., Basak A. N., Beach T., Benitez B. A., Berg D., Bhatia K., Binkofski F., Blauwendraat C., Bonifati V., Borges V., Bozi M., Brice A., Brighina L., Brockmann K., Brucke T., Bruggemann N., Camacho M., Cardoso F., Belin A. C., Carr J., Chan P., Chang-Castello J., Chase B., Chen-Plotkin A., Ju Chung S., Cilia R., Clarimon J., Clark L., Cornejo-Olivas M., Corvol J. -C., Cosentino C., Cras P., Crosiers D., Damasio J., Das P., de Carvalho Aguiar P., De Michele G., De Rosa A., Dieguez E., Dorszewska J., Erer S., Ertan S., Farrer M., Fedotova E., Ferese R., Ferrarese C., Ferraz H., Fiala O., Foroud T., Friedman A., Frigerio R., Funayama M., Gambardella S., Garraux G., Gatto E. M., Genc G., Giladi N., Goldwurm S., Gomez-Esteban J. C., Gomez-Garre P., Gorostidi A., Grosset D., Hanagasi H., Hardy J., Hassan A., Hattori N., Hauser R. A., Hedera P., Hentati F., Hertz J. M., Holton J. L., Houlden H., Hutz M. H., Ikeuchi T., Illarioshkin S., Inca-Martinez M., Infante J., Jankovic J., Jeon B. S., Jesus S., Jimenez-Del-Rio M., Kaasinen V., Kataoka H., Kawakami H., Kim Y. J., Klivenyi P., Koks S., Konig I. R., Kostic V., Koziorowski D., Kruger R., Krygowska-Wajs A., Kulisevsky J., Lai D., Lang A., LeDoux M., Lesage S., Lim S. -Y., Lin C. -H., Lohmann K., Lopera F., Lopez G., Lu C. -S., Lynch T., Machaczka M., Madoev H., Magalhaes M., Majamaa K., Maraganore D., Marder K., Markopoulou K., Martikainen M. H., Mata I., Mazzetti P., Mellick G., Menendez-Gonzalez M., Micheli F., Mirelman A., Mir P., Morino H., Morris H., Munhoz R. P., Naito A., Olszewska D. A., Ozelius L. J., Padmanabhan S., Paisan-Ruiz C., Payami H., Peluso S., Petkovic S., Petrucci S., Pezzoli G., Pimentel M., Pirker W., Pramstaller P. P., Pulkes T., Puschmann A., Quattrone A., Raggio V., Ransmayr G., Rieder C., Riess O., Rodriguez-Porcel F., Rogaeva E., Ross O. A., Ruiz-Martinez J., Sammler E., San Luciano M., Satake W., Saunders-Pullman R., Sazci A., Scherzer C., Schrag A., Schumacher-Schuh A., Sharma M., Sidransky E., Singleton A. B., Petersen M. S., Smolders S., Spitz M., Stefanis L., Struhal W., Sue C. M., Swan M., Swanberg M., Taba P., Taipa R., Tan M., Tan A. H., Tan E. -K., Tang B., Tayebi N., Thaler A., Thomas A., Toda T., Toft M., Torres L., Tumas V., Valente E. M., Van Broeckhoven C., Vecsei L., Velez-Pardo C., Vidailhet M., Warner T. T., Williams-Gray C. H., Winkelmann J., Woitalla D., Wood N. W., Wszolek Z. K., Wu R. -M., Wu Y. -R., Xie T., Yoshino H., Zhang B., and Zimprich A.

Published
2019

10. The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson’s disease and originates from a common ancestor

Author

Goldwurm, S, Fonzo, A Di, Simons, E J, Rohé, C F, Zini, M, Canesi, M, Tesei, S, Zecchinelli, A, Antonini, A, Mariani, C, Meucci, N, Sacilotto, G, Sironi, F, Salani, G, Ferreira, J, Chien, H F, Fabrizio, E, Vanacore, N, Libera, A Dalla, Stocchi, F, Diroma, C, Lamberti, P, Sampaio, C, Meco, G, Barbosa, E, Bertoli-Avella, A M, Breedveld, G J, Oostra, B A, Pezzoli, G, and Bonifati, V

Published
2005

14. Using global team science to identify genetic Parkinson's disease worldwide

Author

Vollstedt, E‐J, Kasten, M., Klein, C., Aasly, J., Adler, C., Ahmad‐Annuar, A., Albanese, A., Alcalay, R., Al‐Mubarak, B., Alvarez, V., Andree‐Muñoz, B., Annesi, G., Appel‐Cresswell, S., Arkadir, D., Armasu, S., Barber, T.R., Bardien, S., Barkhuizen, M., Barrett, M.J., BaŞak, A.N., Beach, T., Benitez, B.A., Berg, D., Bhatia, K., Binkofski, F., Blauwendraat, C., Bonifati, V., Borges, V., Bozi, M., Brice, A., Brighina, L., Brockmann, K., Brüggemann, N., Camacho, M., Cardoso, F., Belin, A.C., Carr, J., Chan, P., Chang‐Castello, J., Chase, B., Chen‐Plotkin, A., Chung, S.J., Cilia, R., Clarimon, J., Clark, L., Cornejo‐Olivas, M., Corvol, J‐C, Cosentino, C., Cras, P., Crosiers, D., Damásio, J., Das, P., Carvalho Aguiar, P., De Michele, G., De Rosa, A., Dieguez, E., Dorszewska, J., Erer, S., Ertan, S., Farrer, M., Fedotova, E., Ferese, R., Ferrarese, C., Ferraz, H., Fiala, O., Foroud, T., Friedman, A., Frigerio, R., Funayama, M., Gambardella, S., Garraux, G., Gatto, E.M., Genç, G., Goldwurm, S., Gomez‐Esteban, J.C., Gómez‐Garre, P., Gorostidi, A., Grosset, D., Hanagasi, H., Hardy, J., Hassan, A., Hattori, N., Hauser, R.A., Hedera, P., Hentati, F., Hertz, J.M., Holton, J.L., Houlden, H., Hutz, M.H., Ikeuchi, T., Illarioshkin, S., Inca‐Martinez, M., Infante, J., Jankovic, J., Jeon, B.S., Jesús, S., Jimenez‐Del‐Rio, M., Kataoka, H., Kawakami, H., Kim, Y.J., Klivényi, P., Kõks, S., König, I.R., KostiĆ, V., Koziorowski, D., Krüger, R., Krygowska‐Wajs, A., Kulisevsky, J., Lang, A., LeDoux, M., Lesage, S., Lim, S‐Y, Lin, C‐H, Lohmann, K., Lopera, F., Lopez, G., Lu, C‐S, Lynch, T., Machaczka, M., Madoev, H., Magalhães, M., Majamaa, K., Maraganore, D., Marder, K., Markopoulou, K., Martikainen, M.H., Mata, I., Mazzetti, P., Mellick, G., Menéndez‐González, M., Micheli, F., Mirelman, A., Mir, P., Morino, H., Morris, H., Munhoz, R.P., Naito, A., Olszewska, D.A., Ozelius, L.J., Padmanabhan, S., Paisán‐Ruiz, C., Payami, H., Peluso, S., Petkovic, S., Petrucci, S., Pezzoli, G., Pimentel, M., Pirker, W., Pramstaller, P.P., Pulkes, T., Puschmann, A., Quattrone, A., Raggio, V., Ransmayr, G., Rieder, C., Riess, O., Rodriguez‐Porcel, F., Rogaeva, E., Ross, O.A., Ruiz‐Martinez, J., Sammler, E., Luciano, M.S., Satake, W., Saunders‐Pullman, R., Sazci, A., Scherzer, C., Schrag, A., Schumacher‐Schuh, A., Sharma, M., Sidransky, E., Singleton, A.B., Petersen, M.S., Smolders, S., Spitz, M., Stefanis, L., Struhal, W., Sue, C., Swan, M., Swanberg, M., Taba, P., Taipa, R., Tan, M., Tan, A.H., Tan, E‐K, Tang, B., Tayebi, N., Thaler, A., Thomas, A., Toda, T., Toft, M., Torres, L., Tumas, V., Valente, E.M., Van Broeckhoven, C., Vecsei, L., Velez‐Pardo, C., Vidailhet, M., Warner, T.T., Williams‐Gray, C.H., Winkelmann, J., Woitalla, D., Wood, N.W., Wszolek, Z.K., Wu, R‐M, Wu, Y‐R, Xie, T., Yoshino, H., Zhang, B., Zimprich, A., Vollstedt, E‐J, Kasten, M., Klein, C., Aasly, J., Adler, C., Ahmad‐Annuar, A., Albanese, A., Alcalay, R., Al‐Mubarak, B., Alvarez, V., Andree‐Muñoz, B., Annesi, G., Appel‐Cresswell, S., Arkadir, D., Armasu, S., Barber, T.R., Bardien, S., Barkhuizen, M., Barrett, M.J., BaŞak, A.N., Beach, T., Benitez, B.A., Berg, D., Bhatia, K., Binkofski, F., Blauwendraat, C., Bonifati, V., Borges, V., Bozi, M., Brice, A., Brighina, L., Brockmann, K., Brüggemann, N., Camacho, M., Cardoso, F., Belin, A.C., Carr, J., Chan, P., Chang‐Castello, J., Chase, B., Chen‐Plotkin, A., Chung, S.J., Cilia, R., Clarimon, J., Clark, L., Cornejo‐Olivas, M., Corvol, J‐C, Cosentino, C., Cras, P., Crosiers, D., Damásio, J., Das, P., Carvalho Aguiar, P., De Michele, G., De Rosa, A., Dieguez, E., Dorszewska, J., Erer, S., Ertan, S., Farrer, M., Fedotova, E., Ferese, R., Ferrarese, C., Ferraz, H., Fiala, O., Foroud, T., Friedman, A., Frigerio, R., Funayama, M., Gambardella, S., Garraux, G., Gatto, E.M., Genç, G., Goldwurm, S., Gomez‐Esteban, J.C., Gómez‐Garre, P., Gorostidi, A., Grosset, D., Hanagasi, H., Hardy, J., Hassan, A., Hattori, N., Hauser, R.A., Hedera, P., Hentati, F., Hertz, J.M., Holton, J.L., Houlden, H., Hutz, M.H., Ikeuchi, T., Illarioshkin, S., Inca‐Martinez, M., Infante, J., Jankovic, J., Jeon, B.S., Jesús, S., Jimenez‐Del‐Rio, M., Kataoka, H., Kawakami, H., Kim, Y.J., Klivényi, P., Kõks, S., König, I.R., KostiĆ, V., Koziorowski, D., Krüger, R., Krygowska‐Wajs, A., Kulisevsky, J., Lang, A., LeDoux, M., Lesage, S., Lim, S‐Y, Lin, C‐H, Lohmann, K., Lopera, F., Lopez, G., Lu, C‐S, Lynch, T., Machaczka, M., Madoev, H., Magalhães, M., Majamaa, K., Maraganore, D., Marder, K., Markopoulou, K., Martikainen, M.H., Mata, I., Mazzetti, P., Mellick, G., Menéndez‐González, M., Micheli, F., Mirelman, A., Mir, P., Morino, H., Morris, H., Munhoz, R.P., Naito, A., Olszewska, D.A., Ozelius, L.J., Padmanabhan, S., Paisán‐Ruiz, C., Payami, H., Peluso, S., Petkovic, S., Petrucci, S., Pezzoli, G., Pimentel, M., Pirker, W., Pramstaller, P.P., Pulkes, T., Puschmann, A., Quattrone, A., Raggio, V., Ransmayr, G., Rieder, C., Riess, O., Rodriguez‐Porcel, F., Rogaeva, E., Ross, O.A., Ruiz‐Martinez, J., Sammler, E., Luciano, M.S., Satake, W., Saunders‐Pullman, R., Sazci, A., Scherzer, C., Schrag, A., Schumacher‐Schuh, A., Sharma, M., Sidransky, E., Singleton, A.B., Petersen, M.S., Smolders, S., Spitz, M., Stefanis, L., Struhal, W., Sue, C., Swan, M., Swanberg, M., Taba, P., Taipa, R., Tan, M., Tan, A.H., Tan, E‐K, Tang, B., Tayebi, N., Thaler, A., Thomas, A., Toda, T., Toft, M., Torres, L., Tumas, V., Valente, E.M., Van Broeckhoven, C., Vecsei, L., Velez‐Pardo, C., Vidailhet, M., Warner, T.T., Williams‐Gray, C.H., Winkelmann, J., Woitalla, D., Wood, N.W., Wszolek, Z.K., Wu, R‐M, Wu, Y‐R, Xie, T., Yoshino, H., Zhang, B., and Zimprich, A.

Abstract

Talks on rare diseases in the field of neurology often start with a statement like this: “About 80% of all rare diseases have a neurologic manifestation and about 80% of those are genetic in origin.” Although these numbers probably represent more of an estimate than well‐documented evidence, rapidly advancing and cost‐effective sequencing technologies have led to the quickly growing identification of patients with hereditary neurological diseases...

Published
2019

15. Using global team science to identify genetic parkinson's disease worldwide

Author

Vollstedt, E. -J., Kasten, M., Klein, C., Aasly, J., Adler, C., Ahmad-Annuar, A., Albanese, Alberto, Alcalay, R. N., Al-Mubarak, B., Alvarez, V., Andree-Munoz, B., Annesi, G., Appel-Cresswell, S., Arkadir, D., Armasu, S., Barber, T. R., Bardien, S., Barkhuizen, M., Barrett, M. J., Basak, A. N., Beach, T., Benitez, B. A., Berg, D., Bhatia, K., Binkofski, F., Blauwendraat, C., Bonifati, V., Borges, V., Bozi, M., Brice, A., Brighina, L., Brockmann, K., Brucke, T., Bruggemann, N., Camacho, M., Cardoso, F., Belin, A. C., Carr, J., Chan, P., Chang-Castello, J., Chase, B., Chen-Plotkin, A., Ju Chung, S., Cilia, R., Clarimon, J., Clark, L., Cornejo-Olivas, M., Corvol, J. -C., Cosentino, C., Cras, P., Crosiers, D., Damasio, J., Das, P., de Carvalho Aguiar, P., De Michele, G., De Rosa, A., Dieguez, E., Dorszewska, J., Erer, S., Ertan, S., Farrer, M., Fedotova, E., Ferese, R., Ferrarese, C., Ferraz, H., Fiala, O., Foroud, T., Friedman, A., Frigerio, R., Funayama, M., Gambardella, S., Garraux, G., Gatto, E. M., Genc, G., Giladi, N., Goldwurm, S., Gomez-Esteban, J. C., Gomez-Garre, P., Gorostidi, A., Grosset, D., Hanagasi, H., Hardy, J., Hassan, A., Hattori, N., Hauser, R. A., Hedera, P., Hentati, F., Hertz, J. M., Holton, J. L., Houlden, H., Hutz, M. H., Ikeuchi, T., Illarioshkin, S., Inca-Martinez, M., Infante, J., Jankovic, J., Jeon, B. S., Jesus, S., Jimenez-Del-Rio, M., Kaasinen, V., Kataoka, H., Kawakami, H., Kim, Y. J., Klivenyi, P., Koks, S., Konig, I. R., Kostic, V., Koziorowski, D., Kruger, R., Krygowska-Wajs, A., Kulisevsky, J., Lai, D., Lang, A., Ledoux, M., Lesage, S., Lim, S. -Y., Lin, C. -H., Lohmann, K., Lopera, F., Lopez, G., Lu, C. -S., Lynch, T., Machaczka, M., Madoev, H., Magalhaes, M., Majamaa, K., Maraganore, D., Marder, K., Markopoulou, K., Martikainen, M. H., Mata, I., Mazzetti, P., Mellick, G., Menendez-Gonzalez, M., Micheli, F., Mirelman, A., Mir, P., Morino, H., Morris, H., Munhoz, R. P., Naito, A., Olszewska, D. A., Ozelius, L. J., Padmanabhan, S., Paisan-Ruiz, C., Payami, H., Peluso, S., Petkovic, S., Petrucci, S., Pezzoli, G., Pimentel, M., Pirker, W., Pramstaller, P. P., Pulkes, T., Puschmann, A., Quattrone, A., Raggio, V., Ransmayr, G., Rieder, C., Riess, O., Rodriguez-Porcel, F., Rogaeva, E., Ross, O. A., Ruiz-Martinez, J., Sammler, E., San Luciano, M., Satake, W., Saunders-Pullman, R., Sazci, A., Scherzer, C., Schrag, A., Schumacher-Schuh, A., Sharma, M., Sidransky, E., Singleton, A. B., Petersen, M. S., Smolders, S., Spitz, M., Stefanis, L., Struhal, W., Sue, C. M., Swan, M., Swanberg, M., Taba, P., Taipa, R., Tan, M., Tan, A. H., Tan, E. -K., Tang, B., Tayebi, N., Thaler, A., Thomas, A., Toda, T., Toft, M., Torres, L., Tumas, V., Valente, E. M., Van Broeckhoven, C., Vecsei, L., Velez-Pardo, C., Vidailhet, M., Warner, T. T., Williams-Gray, C. H., Winkelmann, J., Woitalla, D., Wood, N. W., Wszolek, Z. K., Wu, R. -M., Wu, Y. -R., Xie, T., Yoshino, H., Zhang, B., Zimprich, A., Albanese A. (ORCID:0000-0002-5864-0006), Vollstedt, E. -J., Kasten, M., Klein, C., Aasly, J., Adler, C., Ahmad-Annuar, A., Albanese, Alberto, Alcalay, R. N., Al-Mubarak, B., Alvarez, V., Andree-Munoz, B., Annesi, G., Appel-Cresswell, S., Arkadir, D., Armasu, S., Barber, T. R., Bardien, S., Barkhuizen, M., Barrett, M. J., Basak, A. N., Beach, T., Benitez, B. A., Berg, D., Bhatia, K., Binkofski, F., Blauwendraat, C., Bonifati, V., Borges, V., Bozi, M., Brice, A., Brighina, L., Brockmann, K., Brucke, T., Bruggemann, N., Camacho, M., Cardoso, F., Belin, A. C., Carr, J., Chan, P., Chang-Castello, J., Chase, B., Chen-Plotkin, A., Ju Chung, S., Cilia, R., Clarimon, J., Clark, L., Cornejo-Olivas, M., Corvol, J. -C., Cosentino, C., Cras, P., Crosiers, D., Damasio, J., Das, P., de Carvalho Aguiar, P., De Michele, G., De Rosa, A., Dieguez, E., Dorszewska, J., Erer, S., Ertan, S., Farrer, M., Fedotova, E., Ferese, R., Ferrarese, C., Ferraz, H., Fiala, O., Foroud, T., Friedman, A., Frigerio, R., Funayama, M., Gambardella, S., Garraux, G., Gatto, E. M., Genc, G., Giladi, N., Goldwurm, S., Gomez-Esteban, J. C., Gomez-Garre, P., Gorostidi, A., Grosset, D., Hanagasi, H., Hardy, J., Hassan, A., Hattori, N., Hauser, R. A., Hedera, P., Hentati, F., Hertz, J. M., Holton, J. L., Houlden, H., Hutz, M. H., Ikeuchi, T., Illarioshkin, S., Inca-Martinez, M., Infante, J., Jankovic, J., Jeon, B. S., Jesus, S., Jimenez-Del-Rio, M., Kaasinen, V., Kataoka, H., Kawakami, H., Kim, Y. J., Klivenyi, P., Koks, S., Konig, I. R., Kostic, V., Koziorowski, D., Kruger, R., Krygowska-Wajs, A., Kulisevsky, J., Lai, D., Lang, A., Ledoux, M., Lesage, S., Lim, S. -Y., Lin, C. -H., Lohmann, K., Lopera, F., Lopez, G., Lu, C. -S., Lynch, T., Machaczka, M., Madoev, H., Magalhaes, M., Majamaa, K., Maraganore, D., Marder, K., Markopoulou, K., Martikainen, M. H., Mata, I., Mazzetti, P., Mellick, G., Menendez-Gonzalez, M., Micheli, F., Mirelman, A., Mir, P., Morino, H., Morris, H., Munhoz, R. P., Naito, A., Olszewska, D. A., Ozelius, L. J., Padmanabhan, S., Paisan-Ruiz, C., Payami, H., Peluso, S., Petkovic, S., Petrucci, S., Pezzoli, G., Pimentel, M., Pirker, W., Pramstaller, P. P., Pulkes, T., Puschmann, A., Quattrone, A., Raggio, V., Ransmayr, G., Rieder, C., Riess, O., Rodriguez-Porcel, F., Rogaeva, E., Ross, O. A., Ruiz-Martinez, J., Sammler, E., San Luciano, M., Satake, W., Saunders-Pullman, R., Sazci, A., Scherzer, C., Schrag, A., Schumacher-Schuh, A., Sharma, M., Sidransky, E., Singleton, A. B., Petersen, M. S., Smolders, S., Spitz, M., Stefanis, L., Struhal, W., Sue, C. M., Swan, M., Swanberg, M., Taba, P., Taipa, R., Tan, M., Tan, A. H., Tan, E. -K., Tang, B., Tayebi, N., Thaler, A., Thomas, A., Toda, T., Toft, M., Torres, L., Tumas, V., Valente, E. M., Van Broeckhoven, C., Vecsei, L., Velez-Pardo, C., Vidailhet, M., Warner, T. T., Williams-Gray, C. H., Winkelmann, J., Woitalla, D., Wood, N. W., Wszolek, Z. K., Wu, R. -M., Wu, Y. -R., Xie, T., Yoshino, H., Zhang, B., Zimprich, A., and Albanese A. (ORCID:0000-0002-5864-0006)

Abstract

Talks on rare diseases in the field of neurology often start with a statement like this: “About 80% of all rare diseases have a neurologic manifestation and about 80% of those are genetic in origin.” Although these numbers probably represent more of an estimate than well-documented evidence, rapidly advancing and cost-effective sequencing technologies have led to the quickly growing identification of patients with hereditary neurological diseases. Although the importance of genetics for diagnosis and genetic counseling is undisputed, the recent development of first genetargeted therapies entering clinical trial1,2 is adding an important new layer to the (re-)consideration of genetic testing in neurology. However, establishing accurate genotype– phenotype and genotype–treatment relationships requires large sample sizes. Systematic reviews can serve as instruments to combine information from several small samples, but unfortunately, this is often complicated by inconsistent and incomplete reporting of clinical and genetic data across studies. Thus, large multicenter approaches are necessary to systematically and uniformly characterize patients with genetic neurologic conditions and to eventually establish sizable clinical trial-ready cohorts.

Published
2019

16. Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes

Author

Bonifati V., Rohe C. F., Breedveld G. J., Fabrizio E., De Mari M., Tassorelli C., Tavella A., Marconi R., Nicholl D. J., Chien H. F., Fincati E., Abbruzzese G., Marini P., De Gaetano A., Horstink M. W., Maat Kievit J. A., Sampaio C., Antonini A., Stocchi F., Toni V., Guidi M., Dalla Libera A., Tinazzi M., De Pandis F., Fabbrini G., Goldwurm S., de Klein A., Barbosa E., Lopiano L., Martignoni E., Lamberti P., Vanacore N., Meco G., Oostra B.A., Italian Parkinson Genetics Network, MONTAGNA, PASQUALE, Bonifati V., Rohe C.F., Breedveld G.J., Fabrizio E., De Mari M., Tassorelli C., Tavella A., Marconi R., Nicholl D.J., Chien H.F., Fincati E., Abbruzzese G., Marini P., De Gaetano A., Horstink M.W., Maat-Kievit J.A., Sampaio C., Antonini A., Stocchi F., Montagna P., Toni V., Guidi M., Dalla Libera A., Tinazzi M., De Pandis F., Fabbrini G., Goldwurm S., de Klein A., Barbosa E., Lopiano L., Martignoni E., Lamberti P., Vanacore N., Meco G., Oostra BA., Italian Parkinson Genetics Network., and Clinical Genetics

Subjects
Adult, Male, DNA, Complementary, Adolescent, Genotype, Parkinson's disease, assessment, DNA Mutational Analysis, Mutation, Missense, Biology, Early-onset parkinsonism, medicine.disease_cause, Genotype-phenotype distinction, Cognitive neurosciences [UMCN 3.2], Gene Frequency, PINK1 gene mutations, medicine, Missense mutation, Humans, Genetic Predisposition to Disease, Genetic Testing, Allele, Age of Onset, Child, Allele frequency, Genetics, Mutation, Parkinson'disease, Genome, Polymorphism, Genetic, Sequence Homology, Amino Acid, Parkinsonism, Parkinson Disease, Middle Aged, medicine.disease, Phenotype, Italy, Female, Neurology (clinical), Age of onset, Protein Kinases
Abstract

Item does not contain fulltext OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (

Published
2005

17. Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Author

Wang, L, Aasly, J, Annesi, G, Bardien, S, Bozi, M, Brice, A, Carr, J, Chung, S, Clarke, C, Crosiers, D, Deutschländer, A, Eckstein, G, Farrer, M, Goldwurm, S, Garraux, G, Hadjigeorgiou, G, Hicks, A, Hattori, N, Klein, C, Jeon, B, Kim, Y, Lesage, S, Lin, J, Lynch, T, Lichtner, P, Lang, A, Mok, V, Jasinska-Myga, B, Mellick, G, Morrison, K, Opala, G, Pihlstrøm, L, Pramstaller, P, Park, S, Quattrone, A, Rogaeva, E, Ross, O, Stefanis, L, Stockton, J, Silburn, P, Theuns, J, Tan, E, Tomiyama, H, Toft, M, Van Broeckhoven, C, Uitti, R, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Yueh, K, Zhao, Y, Gasser, T, Maraganore, D, Krüger, R, Sharma, M, Boyle, RS, Sellbach, A, O'Sullivan, JD, Sutherland, GT, Siebert, GA, Dissanayaka, NN, Pickut, B, Engelborghs, S, Meeus, B, De Deyn, PP, Cras, P, Lang, AE, Tzourio, C, Amouyel, P, Loriot, MA, Mutez, E, Duflot, A, Legendre, JP, Waucquier, N, Riess, O, Berg, D, Schulte, C, Djarmati, A, Hagenah, J, Lohman, K, Auburger, G, Hilker, R, van de Loo, S, Dardiotis, E, Tsimourtou, V, Ralli, S, Kountra, P, Patramani, G, Vogiatzi, C, Funayama, M, Yoshino, H, Li, Y, Imamichi, Y, Toda, T, Satake, W, Valente, EM, Ferraris, A, Dallapiccola, B, Ialongo, T, Brighina, L, Corradi, B, Ferrarese, C, Piolti, MR, Tarantino, P, Annesi, F, Gagliardi, M, Jeon, BS, Klodowska-Duda, G, Boczarska-Jedynak, M, Tan, EK, Belin, AC, Olson, L, Galter, D, Westerlund, M, Sydow, O, Nilsson, C, Puschmann, A, Lin, JJ, Maraganore, DM, Ahlskog, J, de Andrade, M, Lesnick, TG, Rocca, WA, Checkowa, H, Ross, OA, Wszolek, ZK, Uitti, RJ, Pathologic Biochemistry and Physiology, GEO-PD Consortium, Wang, L, Aasly, J, Annesi, G, Bardien, S, Bozi, M, Brice, A, Carr, J, Chung, S, Clarke, C, Crosiers, D, Deutschländer, A, Eckstein, G, Farrer, M, Goldwurm, S, Garraux, G, Hadjigeorgiou, G, Hicks, A, Hattori, N, Klein, C, Jeon, B, Kim, Y, Lesage, S, Lin, J, Lynch, T, Lichtner, P, Lang, A, Mok, V, Jasinska-Myga, B, Mellick, G, Morrison, K, Opala, G, Pihlstrøm, L, Pramstaller, P, Park, S, Quattrone, A, Rogaeva, E, Ross, O, Stefanis, L, Stockton, J, Silburn, P, Theuns, J, Tan, E, Tomiyama, H, Toft, M, Van Broeckhoven, C, Uitti, R, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Yueh, K, Zhao, Y, Gasser, T, Maraganore, D, Krüger, R, Sharma, M, Boyle, R, Sellbach, A, O'Sullivan, J, Sutherland, G, Siebert, G, Dissanayaka, N, Pickut, B, Engelborghs, S, Meeus, B, De Deyn, P, Cras, P, Tzourio, C, Amouyel, P, Loriot, M, Mutez, E, Duflot, A, Legendre, J, Waucquier, N, Riess, O, Berg, D, Schulte, C, Djarmati, A, Hagenah, J, Lohman, K, Auburger, G, Hilker, R, van de Loo, S, Dardiotis, E, Tsimourtou, V, Ralli, S, Kountra, P, Patramani, G, Vogiatzi, C, Funayama, M, Yoshino, H, Li, Y, Imamichi, Y, Toda, T, Satake, W, Valente, E, Ferraris, A, Dallapiccola, B, Ialongo, T, Brighina, L, Corradi, B, Ferrarese, C, Piolti, M, Tarantino, P, Annesi, F, Gagliardi, M, Klodowska-Duda, G, Boczarska-Jedynak, M, Belin, A, Olson, L, Galter, D, Westerlund, M, Sydow, O, Nilsson, C, Puschmann, A, Ahlskog, J, de Andrade, M, Lesnick, T, Rocca, W, and Checkowa, H

Subjects
Male, Age at onset, confidence interval, Genetic Epidemiology of Parkinson's Disease, Parkinson disease, spinocerebellar ataxia, Nerve Tissue Proteins, Disease, Biology, Parkinson Disease/epidemiology, Trinucleotide Repeat Expansion/genetics, Gene Frequency, Ataxins/genetics, Humans, Nerve Tissue Proteins/genetics, Genetic Predisposition to Disease, Risk factor, Allele frequency, Nuclear Protein, Aged, risk, Genetics, Medicine(all), Nuclear Proteins, Parkinson Disease, Ataxin, Odds ratio, Middle Aged, Phenotype, Nuclear Proteins/genetics, Genetic epidemiology, Ataxins, Gene Frequency/genetics, Nerve Tissue Protein, Peptide, Cohort, Female, Neurology (clinical), Human medicine, Trinucleotide repeat expansion, Peptides, Trinucleotide Repeat Expansion, Peptides/genetics, Human
Abstract

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson9s Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.

Published
2015
Full Text
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18. Study of alpha-synuclein and its catabolic pathways in ex vivo cells of patients with Parkinson’s disease

Author

SALA, GESSICA, RIVA, CHIARA, STEFANONI, GIOVANNI, AROSIO, ALESSANDRO, MARINIG, DANIELE, BRIGHINA, LAURA, FERRARESE, CARLO, Goldwurm, S, Sala, G, Riva, C, Stefanoni, G, Arosio, A, Marinig, D, Goldwurm, S, Brighina, L, and Ferrarese, C

Subjects
Lamp2a, Hsc70, Chaperone-mediated autophagy, Parkinson's disease, Peripheral blood mononuclear cell, MEF2D
Abstract

Parkinson’s disease (PD) is pathologically characterized by the presence of neuronal inclusions known as Lewy bodies, composed primarily of alpha-synuclein (asyn) aggregates. Emerging data indicate that a dysregulation of the autophagic-lysosomal pathway plays a critical pathogenic role in PD, favoring the intraneuronal accumulation of asyn and other neurotoxic proteins. Besides macroautophagy alterations, dysfunctions of chaperone-mediated autophagy (CMA), the main catabolic pathway for asyn, have been reported in post-mortem brain samples obtained from PD patients. To verify the presence of possible systemic alterations of CMA mirroring those observed in diseased brain areas, the expression of CMA effectors (lamp2A e hsc70) and substrates (asyn and MEF2D) was evaluated in peripheral blood mononuclear cells (PBMC) from PD patients and compared to healthy and neurological controls. Similar analyses are ongoing in fibroblast cell lines obtained from sporadic and familial (LRRK2 and SNCA mutant) PD patients obtained from the “Parkinson Institute Biobank” (Milan, http://www.parkinsonbiobank.com/). Results from this study will allow the identification of new possible PD biomarkers useful for early diagnosis, personalized therapy and monitoring of drug efficacy in clinical trials.

Published
2015

19. A genome-wide association study in multiple system atrophy

Author

Sailer, A, Scholz, SW, Nalls, MA, Schulte, C, Federoff, M, Price, TR, Lees, A, Ross, OA, Dickson, DW, Mok, K, Mencacci, NE, Schottlaender, L, Chelban, V, Ling, H, O'Sullivan, SS, Wood, NW, Traynor, BJ, Ferrucci, L, Federoff, HJ, Mhyre, TR, Morris, HR, Deuschl, G, Quinn, N, Widner, H, Albanese, A, Infante, J, Bhatia, KP, Poewe, W, Oertel, W, Hoglinger, GU, Wullner, U, Goldwurm, S, Pellecchia, MT, Ferreira, J, Tolosa, E, Bloem, BR, Rascol, O, Meissner, WG, Hardy, JA, Revesz, T, Holton, JL, Gasser, T, Wenning, GK, Singleton, AB, Houlden, H, Atrophy, EMS, and Grp, UMSAS

Published
2016
Full Text
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20. Analysis of nucleotide variations in genes of iron management in patients of Parkinson's disease and other movement disorders

Author

Castiglioni E, Finazzi D, Goldwurm S, Pezzoli G, Nardocci N, Forni G, Girelli D, Maccarinelli F, Poli M, FERRARI , MAURIZIO, Cremonesi L, Arosio P., Castiglioni, E, Finazzi, D, Goldwurm, S, Pezzoli, G, Nardocci, N, Forni, G, Girelli, D, Maccarinelli, F, Poli, M, Ferrari, Maurizio, Cremonesi, L, and Arosio, P.

Subjects
Parkinson's disease, Movement disorders, Article Subject, Neurodegeneration with brain iron accumulation, Neuroscience (miscellaneous), Parkinson disease, genetic mutations, Disease, Genes of Iron Management, genetic mutations, Bioinformatics, lcsh:RC346-429, Nucleotide Variations, Parkinson's Disease, Movement Disorders, Hepcidin, Medicine, Restless legs syndrome, lcsh:Neurology. Diseases of the nervous system, Hemojuvelin, biology, business.industry, Hemopexin, medicine.disease, Parkinson disease, Psychiatry and Mental health, biology.protein, Neurology (clinical), medicine.symptom, business, Research Article
Abstract

The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest.

Published
2010

21. Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Author

Wang, L. Aasly, J.O. Annesi, G. Bardien, S. Bozi, M. Brice, A. Carr, J. Chung, S.J. Clarke, C. Crosiers, D. Deutschländer, A. Eckstein, G. Farrer, M.J. Goldwurm, S. Garraux, G. Hadjigeorgiou, G.M. Hicks, A.A. Hattori, N. Klein, C. Jeon, B. Kim, Y.J. Lesage, S. Lin, J.-J. Lynch, T. Lichtner, P. Lang, A.E. Mok, V. Jasinska-Myga, B. Mellick, G.D. Morrison, K.E. Opala, G. PihlstrØm, L. Pramstaller, P.P. Park, S.S. Quattrone, A. Rogaeva, E. Ross, O.A. Stefanis, L. Stockton, J.D. Silburn, P.A. Theuns, J. Tan, E.K. Tomiyama, H. Toft, M. Van Broeckhoven, C. Uitti, R.J. Wirdefeldt, K. Wszolek, Z. Xiromerisiou, G. Yueh, K.-C. Zhao, Y. Gasser, T. Maraganore, D.M. Krüger, R. Sharma, M.

Abstract

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. © 2015 American Academy of Neurology.

Published
2015

22. NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

Author

Blauwendraat, C., Faghri, F., Pihlstrom, L., Geiger, J. T., Elbaz, A., Lesage, S., Corvol, J. -C., May, P., Nicolas, A., Abramzon, Y., Murphy, N. A., Gibbs, J. R., Ryten, M., Ferrari, R., Bras, J., Guerreiro, R., Williams, J., Sims, R., Lubbe, S., Hernandez, D. G., Mok, K. Y., Robak, L., Campbell, R. H., Rogaeva, E., Traynor, B. J., Chia, R., Chung, S. J., Hardy, J. A., Brice, A., Wood, N. W., Houlden, H., Shulman, J. M., Morris, H. R., Gasser, T., Kruger, R., Heutink, P., Sharma, M., Simon-Sanchez, J., Nalls, M. A., Singleton, A. B., Scholz, S. W., Noyce, A. J., Giri, A., Oehmig, A., Tucci, A., Schulte, C., Cookson, M. R., Kia, D., Danjou, F., Charlesworth, G., Plun-Favreau, H., Holmans, P., Jansen, I., Hardy, J., Bras, J. M., Quinn, J., Botia, J. A., Billingsley, K., R'Bibo, L., Lungu, C., Martinez, M., Escott-Price, V., Mencacci, N. E., Topley, Lewis, Denny, P., Rizzu, P., Taba, P., Lovering, R., Ogalla, R. D., Foulger, R., Finkbeiner, S., Sveinbjornsdottir, S., Scholz, S., Koks, S., Foltynie, T., Price, T. R., Sheerin, U. -M., Williams, N., Reed, X., Wang, L., Brockmann, K., Oertel, W., Klein, C., Mohamed, F., Malard, L., Corti, O., Drouet, V., Goldwurm, S., Tesei, S., Canesi, M., Valente, E. M., Petrucci, S., Ginevrino, M., Toft, M., Aasly, J., Henriksen, S. P., Saetehaug, C., Orr-Urtreger, A., Giladi, N., Ferreira, J., Guedes, L. C., Bouca-Machado, R., Coelho, M., Rosa, M. M., Tolosa, E., Fernandez-Santiago, R., Ezquerra, M., Marti, M. J., Glaab, E., Balling, R., and Chung, S. -J.

Subjects
0301 basic medicine, Aging, methods [Genome-Wide Association Study], 0302 clinical medicine, Corticobasal degeneration, neurodegenerative diseases, humans, risk, high-throughput screening assays, education.field_of_study, General Neuroscience, neurodegeneration, genetics [Genetic Variation], 3. Good health, Neurochip, alleles, methods [Genotyping Techniques], Frontotemporal dementia, Risk, Population, methods [High-Throughput Screening Assays], Computational biology, Genetic screening, genotyping, NeuroChip, NeuroX, apolipoproteins E, genetic variation, genome-wide association study, genotyping techniques, Article, Progressive supranuclear palsy, 03 medical and health sciences, Apolipoproteins E, medicine, Humans, Dementia, ddc:610, education, Genotyping, Alleles, business.industry, medicine.disease, 030104 developmental biology, genetics [Neurodegenerative Diseases], genetics [Apolipoproteins E], Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, 030217 neurology & neurosurgery, Imputation (genetics), Developmental Biology
Abstract

Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy. The tagging backbone was chosen because of the low cost and good genome-wide resolution; the custom content can be combined with other backbones, like population or drug development arrays. Using the NeuroChip, we can accurately identify rare variants and impute over 5.3 million common SNPs from the latest release of the Haplotype Reference Consortium. In summary, we describe the design and usage of the NeuroChip array and show its capability for detecting rare pathogenic variants in numerous neurodegenerative diseases. The NeuroChip has a more comprehensive and improved content, which makes it a reliable, high-throughput, cost-effective screening tool for genetic research and molecular diagnostics in neurodegenerative diseases.

Published
2017
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23. PINK1 mutations cause typical late-onset Parkinson's disease as well as early-onset Parkinsonism

Author

Ialongo T., Marongiu R., Ferraris A., Ghezzi D., Soleti F., Elia A., Cavone S., Michiorri S., Albanese A., Altavista M. C., Antonini A., Barone P, Bonuccelli U., Brusa L., Goldwurm S., Pellecchia M. T., Pezzoli G., Stanzione P., Tinazzi M., Zeviani M., Dalla Piccola B., Garavaglia B., Bentivoglio A. R., Valente E. M., CORTELLI, PIETRO, MARTINELLI, PAOLO, SCAGLIONE, CESA LORELLA MARIA, Ialongo T., Marongiu R., Ferraris A., Ghezzi D., Soleti F., Elia A., Cavone S., Michiorri S., Albanese A., Altavista M.C., Antonini A., Barone P, Bonuccelli U., Brusa L., Cortelli P., Goldwurm S., Martinelli P., Pellecchia M.T., Pezzoli G., Scaglione C., Stanzione P., Tinazzi M., Zeviani M., Dalla Piccola B., Garavaglia B., Bentivoglio A.R., and Valente E.M.

Published
2006

24. A genome-wide association study in multiple system atrophy

Author

Sailer, A., Scholz, S.W., Nalls, M.A., Schulte, C., Federoff, M., Price, T.R., Lees, A., Ross, O.A., Dickson, D.W., Mok, K., Mencacci, N.E., Schottlaender, L., Chelban, V., Ling, H., O'Sullivan, S.S, Wood, N.W., Traynor, B.J., Ferrucci, L., Federoff, H.J., Mhyre, T.R., Morris, H.R., Deuschl, G., Quinn, N., Widner, H., Albanese, A., Infante, J., Bhatia, K.P., Poewe, W., Oertel, W., Hoglinger, G.U., Wullner, U., Goldwurm, S., Pellecchia, M.T., Ferreira, J., Tolosa, E., Bloem, B.R., Rascol, O., Meissner, W.G., Hardy, J.A., Revesz, T., Holton, J.L., Gasser, T., Wenning, G.K., Singleton, A.B., Houlden, H., Sailer, A., Scholz, S.W., Nalls, M.A., Schulte, C., Federoff, M., Price, T.R., Lees, A., Ross, O.A., Dickson, D.W., Mok, K., Mencacci, N.E., Schottlaender, L., Chelban, V., Ling, H., O'Sullivan, S.S, Wood, N.W., Traynor, B.J., Ferrucci, L., Federoff, H.J., Mhyre, T.R., Morris, H.R., Deuschl, G., Quinn, N., Widner, H., Albanese, A., Infante, J., Bhatia, K.P., Poewe, W., Oertel, W., Hoglinger, G.U., Wullner, U., Goldwurm, S., Pellecchia, M.T., Ferreira, J., Tolosa, E., Bloem, B.R., Rascol, O., Meissner, W.G., Hardy, J.A., Revesz, T., Holton, J.L., Gasser, T., Wenning, G.K., Singleton, A.B., and Houlden, H.

Abstract

Contains fulltext : 167706.pdf (publisher's version ) (Open Access), OBJECTIVE: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). METHODS: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. RESULTS: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 x 10-6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. CONCLUSIONS: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.

Published
2016

25. PINK1 mutations in a large cohort of Italian patients with early and late-onset parkinsonism

Author

Ialongo T., Marongiu R., Soleti F., Michiorri S., Ghezzi D., Garavaglia B., Pezzoli G., Goldwurm S., Brusa L., Tinazzi M., Barone P., Bonuccelli U., Altavista M. C., Dallapiccola B., Albanese A., Valente E. M., Bentivoglio A. R., CORTELLI, PIETRO, MARTINELLI, PAOLO, Ialongo T., Marongiu R., Soleti F., Michiorri S., Ghezzi D., Garavaglia B., Pezzoli G., Goldwurm S., Brusa L., Tinazzi M., Barone P., Cortelli P., Bonuccelli U., Altavista M.C., Martinelli P., Dallapiccola B., Albanese A., Valente E.M., and Bentivoglio A.R.

Subjects
PINK1, PARKINSONISM
Published
2005

26. Analisi mutazionale del gene pink1 in una vasta casistica di pazienti italiani

Author

Ialongo T., Marongiu R., Soleti F., Ghezzi D., Garavaglia B., Pezzoli G., Goldwurm S., Brusa L., Tinazzi M., Barone P., Bonuccelli U., Altavista M. C., Dallapiccola B., Albanese A., Valente E. M., Bentivoglio A. R., CORTELLI, PIETRO, MARTINELLI, PAOLO, BERGAMASCO B., CORSINI G.U., NAPPI G., RUGGIERI S., SPANO PF., Ialongo T., Marongiu R., Soleti F., Ghezzi D., Garavaglia B., Pezzoli G., Goldwurm S., Brusa L., Tinazzi M., Barone P., Cortelli P., Bonuccelli U., Altavista M.C., Martinelli P., Dallapiccola B., Albanese A., Valente E.M., and Bentivoglio A.R.

Subjects
GENETICA, PINK 1, MALATTIA DI PARKINSON
Published
2005

27. Mutant COQ2 in multiple-system atrophy

Author

Sharma, M, Wenning, G, Krüger, R, European Multiple-System Atrophy Study Group (Sharma, M, Lichtner, P, Albanese, Donatella, Barone, P, Berciano, J, Bloem, Br, Coelho, M, Goldwurm, S, Infante, J, Klockgether, T, Ortega-Cubero, S, Del Sorbo, F, Pezzoli, G, Canesi, M, Tesei, S, Zecchinelli, A, Sacilotto, G, Meucci, N, Mariani, C, Cilia, R, Zini, M, Siri, C, Pellecchia, Mt, Picillo, M, Amboni, M, Schulte, C, Martí, Mj, Sampaio, C, Ferreira, J, Levin, J, Nilsson, Cf, Widner, H, Østergaard, K, Oertel, W, Pastor, P, Storch, A, Seppi, K, Geser, F, Krismer, F, Mahlknecht, P, Sprenger, Fs, Schöls, L, Tolosa, E, Wüllner, U, van de Warrenburg BP, Poewe, W, Gasser, T, and Krüger, R. ).

Subjects
Genetics, Male, Alkyl and Aryl Transferases, Parkinsonism, Copy number analysis, Locus (genetics), General Medicine, Odds ratio, Multiple System Atrophy, Biology, genetics [Alkyl and Aryl Transferases], medicine.disease, 3. Good health, Exon, Atrophy, Start codon, medicine, Humans, Female, ddc:610, genetics [Multiple System Atrophy], Gene
Abstract

To the Editor: Tsuji and colleagues (July 18 issue)1 report that variants in the gene encoding coenzyme Q2 (COQ2) increase the risk of multiple-system atrophy. They observed homozygous COQ2 variants encoding the substitutions M78V and V343A in a consanguineous Japanese family with multiple-system atrophy subtype P and noted an association between V343A and sporadic multiple-system atrophy (minor-allele frequency [MAF], 4.8% of cases vs. 1.6% of controls; odds ratio, 3.05; 95% confidence interval, 1.65 to 5.85). However, the authors erroneously labeled human COQ2 variability from the fourth ATG start codon in exon 1, which encodes the smallest protein isoform and does not functionally complement the yeast coq2-null mutant.2 On the basis of the National Center for Biotechnology Information (NCBI) Reference Sequence (NM_015697.7), M78V should be labeled COQ2 c.382A→G (p.M128V) and V343A should be labeled c.1178T→C (p.V393A). We sequenced COQ2 in 299 Korean persons with multiple-system atrophy and 365 unaffected Korean persons and observed heterozygous COQ2 c.320G→C (encoding p.S107T) and c.382A→T (encoding p.M128R) in 2 patients with sporadic multiple-system atrophy; COQ2 c.1178T→C (p.V393A) was not associated with multiple-system atrophy (MAF, 2.7% of cases vs. 2.6% of controls). It is a challenge to reconcile recessive linkage of homozygous COQ2 mutations in familial multiple-system atrophy with a heterozygous, presumably dominant-negative association in sporadic multiple-system atrophy. Respectfully, we suggest that Tsuji and colleagues reconsider whether variations in COQ2 represent a risk factor for multiple-system atrophy. Genomic multiplications of the SNCA 6.4-Mb locus telomeric to COQ2 have previously been implicated in parkinsonism and multiple-system atrophy3; copy number analysis of linked loci, or genomewide analysis, should be considered.

Published
2014
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28. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Author

Nalls, M.A. Pankratz, N. Lill, C.M. Do, C.B. Hernandez, D.G. Saad, M. Destefano, A.L. Kara, E. Bras, J. Sharma, M. Schulte, C. Keller, M.F. Arepalli, S. Letson, C. Edsall, C. Stefansson, H. Liu, X. Pliner, H. Lee, J.H. Cheng, R. Ikram, M.A. Ioannidis, J.P.A. Hadjigeorgiou, G.M. Bis, J.C. Martinez, M. Perlmutter, J.S. Goate, A. Marder, K. Fiske, B. Sutherland, M. Xiromerisiou, G. Myers, R.H. Clark, L.N. Stefansson, K. Hardy, J.A. Heutink, P. Chen, H. Wood, N.W. Houlden, H. Payami, H. Brice, A. Scott, W.K. Gasser, T. Bertram, L. Eriksson, N. Foroud, T. Singleton, A.B. Plagnol, V. Sheerin, U.-M. Simón-Sánchez, J. Lesage, S. Sveinbjörnsdóttir, S. Barker, R. Ben-Shlomo, Y. Berendse, H.W. Berg, D. Bhatia, K. de Bie, R.M.A. Biffi, A. Bloem, B. Bochdanovits, Z. Bonin, M. Bras, J.M. Brockmann, K. Brooks, J. Burn, D.J. Charlesworth, G. Chinnery, P.F. Chong, S. Clarke, C.E. Cookson, M.R. Cooper, J.M. Corvol, J.C. Counsell, C. Damier, P. Dartigues, J.-F. Deloukas, P. Deuschl, G. Dexter, D.T. van Dijk, K.D. Dillman, A. Durif, F. Dürr, A. Edkins, S. Evans, J.R. Foltynie, T. Dong, J. Gardner, M. Gibbs, J.R. Gray, E. Guerreiro, R. Harris, C. van Hilten, J.J. Hofman, A. Hollenbeck, A. Holton, J. Hu, M. Huang, X. Wurster, I. Mätzler, W. Hudson, G. Hunt, S.E. Huttenlocher, J. Illig, T. Jónsson, P.V. Lambert, J.-C. Langford, C. Lees, A. Lichtner, P. Limousin, P. Lopez, G. Lorenz, D. McNeill, A. Moorby, C. Moore, M. Morris, H.R. Morrison, K.E. Mudanohwo, E. O’sullivan, S.S. Pearson, J. Pétursson, H. Pollak, P. Post, B. Potter, S. Ravina, B. Revesz, T. Riess, O. Rivadeneira, F. Rizzu, P. Ryten, M. Sawcer, S. Schapira, A. Scheffer, H. Shaw, K. Shoulson, I. Sidransky, E. Smith, C. Spencer, C.C.A. Stefánsson, H. Bettella, F. Stockton, J.D. Strange, A. Talbot, K. Tanner, C.M. Tashakkori-Ghanbaria, A. Tison, F. Trabzuni, D. Traynor, B.J. Uitterlinden, A.G. Velseboer, D. Vidailhet, M. Walker, R. van de Warrenburg, B. Wickremaratchi, M. Williams, N. Williams-Gray, C.H. Winder-Rhodes, S. Stefánsson, K. Hardy, J. Factor, S. Higgins, D. Evans, S. Shill, H. Stacy, M. Danielson, J. Marlor, L. Williamson, K. Jankovic, J. Hunter, C. Simon, D. Ryan, P. Scollins, L. Saunders-Pullman, R. Boyar, K. Costan-Toth, C. Ohmann, E. Sudarsky, L. Joubert, C. Friedman, J. Chou, K. Fernandez, H. Lannon, M. Galvez-Jimenez, N. Podichetty, A. Thompson, K. Lewitt, P. Deangelis, M. O'brien, C. Seeberger, L. Dingmann, C. Judd, D. Marder, K. Fraser, J. Harris, J. Bertoni, J. Peterson, C. Rezak, M. Medalle, G. Chouinard, S. Panisset, M. Hall, J. Poiffaut, H. Calabrese, V. Roberge, P. Wojcieszek, J. Belden, J. Jennings, D. Marek, K. Mendick, S. Reich, S. Dunlop, B. Jog, M. Horn, C. Uitti, R. Turk, M. Ajax, T. Mannetter, J. Sethi, K. Carpenter, J. Dill, B. Hatch, L. Ligon, K. Narayan, S. Blindauer, K. Abou-Samra, K. Petit, J. Elmer, L. Aiken, E. Davis, K. Schell, C. Wilson, S. Velickovic, M. Koller, W. Phipps, S. Feigin, A. Gordon, M. Hamann, J. Licari, E. Marotta-Kollarus, M. Shannon, B. Winnick, R. Simuni, T. Videnovic, A. Kaczmarek, A. Williams, K. Wolff, M. Rao, J. Cook, M. Fernandez, M. Kostyk, S. Hubble, J. Campbell, A. Reider, C. Seward, A. Camicioli, R. Carter, J. Nutt, J. Andrews, P. Morehouse, S. Stone, C. Mendis, T. Grimes, D. Alcorn-Costa, C. Gray, P. Haas, K. Vendette, J. Sutton, J. Hutchinson, B. Young, J. Rajput, A. Klassen, L. Shirley, T. Manyam, B. Simpson, P. Whetteckey, J. Wulbrecht, B. Truong, D. Pathak, M. Frei, K. Luong, N. Tra, T. Tran, A. Vo, J. Lang, A. Kleiner-Fisman, G. Nieves, A. Johnston, L. So, J. Podskalny, G. Giffin, L. Atchison, P. Allen, C. Martin, W. Wieler, M. Suchowersky, O. Furtado, S. Klimek, M. Hermanowicz, N. Niswonger, S. Shults, C. Fontaine, D. Aminoff, M. Christine, C. Diminno, M. Hevezi, J. Dalvi, A. Kang, U. Richman, J. Uy, S. Sahay, A. Gartner, M. Schwieterman, D. Hall, D. Leehey, M. Culver, S. Derian, T. Demarcaida, T. Thurlow, S. Rodnitzky, R. Dobson, J. Lyons, K. Pahwa, R. Gales, T. Thomas, S. Shulman, L. Weiner, W. Dustin, K. Singer, C. Zelaya, L. Tuite, P. Hagen, V. Rolandelli, S. Schacherer, R. Kosowicz, J. Gordon, P. Werner, J. Serrano, C. Roque, S. Kurlan, R. Berry, D. Gardiner, I. Hauser, R. Sanchez-Ramos, J. Zesiewicz, T. Delgado, H. Price, K. Rodriguez, P. Wolfrath, S. Pfeiffer, R. Davis, L. Pfeiffer, B. Dewey, R. Hayward, B. Johnson, A. Meacham, M. Estes, B. Walker, F. Hunt, V. O'neill, C. Racette, B. Swisher, L. Dijamco, C. Conley, E.D. Dorfman, E. Tung, J.Y. Hinds, D.A. Mountain, J.L. Wojcicki, A. Lew, M. Klein, C. Golbe, L. Growdon, J. Wooten, G.F. Watts, R. Guttman, M. Goldwurm, S. Saint-Hilaire, M.H. Baker, K. Litvan, I. Nicholson, G. Nance, M. Drasby, E. Isaacson, S. Burn, D. Pramstaller, P. Al-Hinti, J. Moller, A. Sherman, S. Roxburgh, R. Slevin, J. Perlmutter, J. Mark, M.H. Huggins, N. Pezzoli, G. Massood, T. Itin, I. Corbett, A. Chinnery, P. Ostergaard, K. Snow, B. Cambi, F. Kay, D. Samii, A. Agarwal, P. Roberts, J.W. Higgins, D.S. Molho, E. Rosen, A. Montimurro, J. Martinez, E. Griffith, A. Kusel, V. Yearout, D. Factor, S. Zabetian, C. Clark, L.N. Liu, X. Lee, J.H. Cheng Taub, R. Louis, E.D. Cote, L.J. Waters, C. Ford, B. Fahn, S. Vance, J.M. Beecham, G.W. Martin, E.R. Nuytemans, K. Pericak-Vance, M.A. Haines, J.L. Destefano, A. Seshadri, S. Choi, S.H. Frank, S. Bis, J.C. Psaty, B.M. Rice, K. Longstreth, W.T., Jr. Ton, T.G.N. Jain, S. van Duijn, C.M. Uitterlinden, A.G. Verlinden, V.J. Koudstaal, P.J. Singleton, A. Cookson, M. Gibbs, J.R. Hernandez, D. Nalls, M. Zonderman, A. Ferrucci, L. Johnson, R. Longo, D. O'brien, R. Traynor, B. Troncoso, J. van der Brug, M. Zielke, R. Weale, M. Ramasamy, A. Dardiotis, E. Tsimourtou, V. Spanaki, C. Plaitakis, A. Bozi, M. Stefanis, L. Vassilatis, D. Koutsis, G. Panas, M. Hadjigeorgiou, G.M. Lunnon, K. Lupton, M. Powell, J. Parkkinen, L. Ansorge, O. International Parkinson's Disease Genomics Consortium (IPDGC) Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI) 23andMe GenePD NeuroGenetics Research Consortium (NGRC) Hussman Institute of Human Genomics (HIHG) The Ashkenazi Jewish Dataset Investigator Cohorts for Health Aging Research in Genetic Epidemiology (CHARGE) North American Brain Expression Consortium (NABEC) United Kingdom Brain Expression Consortium (UKBEC) Greek Parkinson's Disease Consortium Alzheimer Genetic Analysis Group

Abstract

We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10-16). We also show six risk loci associated with proximal gene expression or DNA methylation. © 2014 Nature America, Inc. All rights reserved.

Published
2014

29. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

Author

Höglinger, GU, Melhem, NM, Dickson, DW, Sleiman, PMA, Wang, LS, Klei, L, Rademakers, R, De Silva, R, Litvan, I, Riley, DE, Van Swieten, JC, Heutink, P, Wszolek, ZK, Uitti, RJ, Vandrovcova, J, Hurtig, HI, Gross, RG, Maetzler, W, Goldwurm, S, Tolosa, E, Borroni, B, Pastor, P, Cantwell, LB, Han, MR, Dillman, A, Van Der Brug, MP, Gibbs, JR, Cookson, MR, Hernandez, DG, Singleton, AB, Farrer, MJ, Yu, CE, Golbe, LI, Revesz, T, Hardy, J, Lees, AJ, Devlin, B, Hakonarson, H, Müller, U, Schellenberg, GD, Albin, RL, Alonso, E, Antonini, A, Apfelbacher, M, Arnold, SE, Avila, J, Beach, TG, Beecher, S, Berg, D, Bird, TD, Bogdanovic, N, Boon, AJW, Bordelon, Y, Brice, A, Budka, H, Canesi, M, Chiu, WZ, Cilia, R, Colosimo, C, De Deyn, PP, De Yebenes, JG, Kaat, LD, Duara, R, Durr, A, Engelborghs, S, Fabbrini, G, Finch, NA, Flook, R, Frosch, MP, Gaig, C, Galasko, DR, Gasser, T, Gearing, M, Geller, ET, Ghetti, B, Graff-Radford, NR, Grossman, M, Hall, DA, Hazrati, LN, Höllerhage, M, Jankovic, J, Juncos, JL, Karydas, A, Kretzschmar, HA, and Leber, I

Subjects
eye diseases
Abstract

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals (P < 5 × 10-8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved.

Published
2011
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30. Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Wang, L., Aasly, J. O., Annesi, G., Bardien, S., Bozi, M., Brice, A., Carr, J., Chung, S. J., Clarke, C., Crosiers, D., Deutschlander, A., Eckstein, G., Farrer, M. J., Goldwurm, S., Garraux, G., Hadjigeorgiou, G. M., Hicks, A. A., Hattori, N., Klein, C., Jeon, B., Kim, Y. J., Lesage, S., Lin, J.J., Lynch, T., Lichtner, P., Lang, A.E., Mok, V., Jasinska-Myga, B., Mellick, G. D., Morrison, K. E., Opala, G., Pihlstrom, L., Pramstaller, P. P., Park, S. S., Quattrone, A., Rogaeva, E., Ross, O. A., Stefanis, L., Stockton, J. D., Silburn, P. A., Theuns, J., Tan, E. K., Tomiyama, H., Toft, M., Van Broeckhoven, C., Uitti, R. J., Wirdefeldt, K., Wszolek, Z., Xiromerisiou, G., Yueh, K. C., Zhao, Y., Gasser, T., Maraganore, D. M., Krüger, Rejko, Sharma, M., Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Wang, L., Aasly, J. O., Annesi, G., Bardien, S., Bozi, M., Brice, A., Carr, J., Chung, S. J., Clarke, C., Crosiers, D., Deutschlander, A., Eckstein, G., Farrer, M. J., Goldwurm, S., Garraux, G., Hadjigeorgiou, G. M., Hicks, A. A., Hattori, N., Klein, C., Jeon, B., Kim, Y. J., Lesage, S., Lin, J.J., Lynch, T., Lichtner, P., Lang, A.E., Mok, V., Jasinska-Myga, B., Mellick, G. D., Morrison, K. E., Opala, G., Pihlstrom, L., Pramstaller, P. P., Park, S. S., Quattrone, A., Rogaeva, E., Ross, O. A., Stefanis, L., Stockton, J. D., Silburn, P. A., Theuns, J., Tan, E. K., Tomiyama, H., Toft, M., Van Broeckhoven, C., Uitti, R. J., Wirdefeldt, K., Wszolek, Z., Xiromerisiou, G., Yueh, K. C., Zhao, Y., Gasser, T., Maraganore, D. M., Krüger, Rejko, and Sharma, M.

Abstract

OBJECTIVES: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). METHODS: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. RESULTS: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. CONCLUSIONS: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.

Published
2015

31. Study of alpha-synuclein and its catabolic pathways in ex vivo cells of patients with Parkinson’s disease

Author

Sala, G, Riva, C, Stefanoni, G, Arosio, A, Marinig, D, Goldwurm, S, Brighina, L, Ferrarese, C, SALA, GESSICA, RIVA, CHIARA, STEFANONI, GIOVANNI, AROSIO, ALESSANDRO, MARINIG, DANIELE, BRIGHINA, LAURA, FERRARESE, CARLO, Sala, G, Riva, C, Stefanoni, G, Arosio, A, Marinig, D, Goldwurm, S, Brighina, L, Ferrarese, C, SALA, GESSICA, RIVA, CHIARA, STEFANONI, GIOVANNI, AROSIO, ALESSANDRO, MARINIG, DANIELE, BRIGHINA, LAURA, and FERRARESE, CARLO

Abstract

Parkinson’s disease (PD) is pathologically characterized by the presence of neuronal inclusions known as Lewy bodies, composed primarily of alpha-synuclein (asyn) aggregates. Emerging data indicate that a dysregulation of the autophagic-lysosomal pathway plays a critical pathogenic role in PD, favoring the intraneuronal accumulation of asyn and other neurotoxic proteins. Besides macroautophagy alterations, dysfunctions of chaperone-mediated autophagy (CMA), the main catabolic pathway for asyn, have been reported in post-mortem brain samples obtained from PD patients. To verify the presence of possible systemic alterations of CMA mirroring those observed in diseased brain areas, the expression of CMA effectors (lamp2A e hsc70) and substrates (asyn and MEF2D) was evaluated in peripheral blood mononuclear cells (PBMC) from PD patients and compared to healthy and neurological controls. Similar analyses are ongoing in fibroblast cell lines obtained from sporadic and familial (LRRK2 and SNCA mutant) PD patients obtained from the “Parkinson Institute Biobank” (Milan, http://www.parkinsonbiobank.com/). Results from this study will allow the identification of new possible PD biomarkers useful for early diagnosis, personalized therapy and monitoring of drug efficacy in clinical trials.

Published
2015

34. A voxel-based PET study of dopamine transporters in Parkinson's disease: relevance of age at onset

Author

Panzacchi A. 1, Moresco R.M. 2, 3, Garibotto V. 3, 4, Antonini A. 5, Gobbo C. 1, Isaias I.U. 5, Goldwurm S. 5, Bonaldi L. 2, Carpinelli A. 2, Pezzoli G. 5, Fazio F. 1, 2, and Perani D. 1

Subjects
[11C]FECIT PET, nervous system, Parkinson's disease, Dopamine transporter, Genetics, Age at onset
Abstract

We used positron emission tomography (PET) and the dopamine transporter (DAT) ligand [(11)C]FECIT to measure loss of nigrostriatal dopaminergic neurons in early phase of early onset (EOPD) and late onset Parkinson's disease (LOPD). The analysis was carried out with both regions of interest and voxelwise method (SPM2), at group and single subject levels. Genetic analysis tested for the mutations occurring most frequently in Caucasian population. A significant, bilateral, asymmetric DAT reduction was observed in both EOPD and LOPD. Noteworthy, the side and severity of DAT binding reduction significantly correlated with the severity and asymmetry of motor clinical scores. The two EOPD patients carrying mutations in the PARK2 and PARK6 genes, respectively, displayed the lowest values, bilaterally. This work demonstrates that severity of nigrostriatal damage in early disease phase of sporadic PD is not dependent on age at onset. Genetically determined PD is associated with more severe and widespread dopaminergic impairment.

Published
2008

35. ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease

Author

Di Fonzo, A, Chien, Hf, Socal, M, Giraudo, S, Tassorelli, C, Iliceto, G, Fabbrini, G, Marconi, R, Fincati, E, Abbruzzese, G, Marini, P, Squitieri, F, Horstink, Mw, Montagna, P, Libera, Ad, Stocchi, F, Goldwurm, S, Ferreira, Jj, Meco, G, Martignoni, E, Lopiano, L, Jardim, Lb, Oostra, Ba, Barbosa, Er, Bonifati, V, Vanacore, N, Fabrizio, E, Locuratolo, N, Scoppetta, C, Manfredi, M, Berardelli, A, Bergamasco, B, Pacchetti, C, Nappi, G, Antonini, A, Pezzoli, G, Riboldazzi, G, Bono, G, Raudino, F, Tinazzi, M, Bonizzato, A, Ferracci, C, Dalla Libera, A, Marchese, R, Massaro, F, Guidi, M, Minardi, C, Rasi, F, Onofrj, M, Thomas, A, Vacca, L, De Pandis, F, De Mari, M, Diroma, C, Lamberti, P, Toni, V, Trianni, G, Mauro, A, De Gaetano, A, Rizzo, M, Cossu, G, Rieder, Crm, and Saraivapereira, Ml.

Published
2007

36. ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson's disease

Author

Alessio Di Fonzo, Chien, H., Socal, M., Giraudo, S., Tassorelli, C., Iliceto, G., Fabbrini, G., Marconi, R., Fincati, E., Abruzzese, G., Marini, P., Squitieri, F., Horstink, M. W. I. M., Montagna, P., Dalla Libera, A., Stocchi, F., Goldwurm, S., Ferreira, J., Meco, G., Martignoni, E., Lopiano, L., Jardim, L., Oostra, B. A., Barbosa, E., and Bonifati, V.

Published
2007

37. Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease

Author

Di Fonzo, A, Tassorelli, C, De Mari, M, Chien, Hf, Ferreira, J, Rohé, Cf, Riboldazzi, G, Antonini, A, Albani, G, Mauro, A, Marconi, R, Abbruzzese, G, Lopiano, L, Fincati, E, Guidi, M, Marini, P, Stocchi, F, Onofrj, M, Toni, V, Tinazzi, M, Fabbrini, G, Lamberti, P, Vanacore, N, Meco, G, Leitner, P, Uitti, Rj, Wszolek, Zk, Gasser, T, Simons, Ej, Breedveld, Gj, Goldwurm, S, Pezzoli, G, Sampaio, C, Barbosa, E, Martignoni, E, Oostra, Ba, Bonifati, V, Vancore, N, Fabrizio, E, Locuratolo, N, Martini, L, Scoppetta, C, Colosimo, C, Manfredi, Ma, Tavella, A, Bergamasco, B, Pacchetti, C, Nappi, G, Canesi, M, Calandrella, D, Brono, G, Manfredi, Mi, Raudino, F, Corengia, E, Bonizzato, A, Ferracci, C, Dalla Libera, A, Marchese, R, Montagna, P, Ramat, S, Massaro, F, Minardi, C, Rasi, F, Thomas, A, Vacca, L, De Pandis, F, Diroma, C, Iliceto, G, Trianni, G, De Gaetano, A, Rizzo, M, and Cossu, G.

Published
2006

40. Novel parkin mutations detected in patients with early-onset Parkinson's disease

Author

Bertoli-Avella, Am, Giroud-Benitez, Jl, Akyol, A, Barbosa, E, Schaap, O, van der Linde HC, Martignoni, E, Lopiano, L, Lamberti, P, Fincati, E, Antonini, A, Stocchi, F, Montagna, P, Squitieri, F, Marini, P, Abbruzzese, G, Fabbrini, G, Marconi, R, Dalla Libera, A, Trianni, G, Guidi, M, De Gaetano, A, Boff Maegawa, G, De Leo, A, Gallai, V, de Rosa, G, Vanacore, N, Meco, G, van Duijn CM, Oostra, Ba, Heutink, P, Bonifati, V, Fabrizio, E, Locuratolo, N, Martini, L, Vacca, L, De Pandis, F, Colosimo, C, Manfredi, M, Tavella, A, Bergamasco, B, Tassorelli, C, Pacchetti, C, Nappi, G, Goldwurm, S, Pezzoli, G, Calandrella, D, Riboldazzi, G, Ferrari, G, Tarletti, R, Cantello, R, Marchese, R, Scaglione, C, Martinelli, P, Massaro, F, Minardi, C, Rasi, F, Lanari, A, Brustenghi, P, Cannella, M, de Mari, M, di Roma, C, Iliceto, G, Toni, V, Coppola, G, Mauro, A, Chien, Shf, Dutra, Ap, Nagahashi, Sk, Jardim, L, Rieder, C, Kiylioglu, N, Temocin, K, and Ulucan, H.

Published
2005

44. Mitochondrial DNA haplogroup K in associated with a lower risk of Parkinson's disease in Italians

Author

Ghezzi, D, Marelli, Cecilia, Achilli, A, Goldwurm, S, Pezzoli, G, Barone, P, Pellecchia, Mt, Stanzione, P, Brusa, L, Bentivoglio, Anna Rita, Bonuccelli, U, Petrozzi, L, Abbruzzese, G, Marchese, R, Cortelli, P, Grimaldi, D, Martinelli, P, Ferrarese, C, Garavaglia, B, Sangiorgi, S, Carelli, V, Albanese, Alberto, and Zeviani, M

Subjects
Settore MED/26 - NEUROLOGIA, malattia di Parkinson
Published
2005

45. LRRK2 mutations in Parkinson's disease: Confirmation of a gender effect in the Italian population

Author

Cilia, R, Siri, C, Rusconi, D, Allegra, R, Ghiglietti, A, Sacilotto, G, Zini, M, Zecchinelli, A, Asselta, R, Duga, S, Paganoni, A, Pezzoli, G, Seia, M, Goldwurm, S, Zecchinelli, AL, Paganoni, AM, Cilia, R, Siri, C, Rusconi, D, Allegra, R, Ghiglietti, A, Sacilotto, G, Zini, M, Zecchinelli, A, Asselta, R, Duga, S, Paganoni, A, Pezzoli, G, Seia, M, Goldwurm, S, Zecchinelli, AL, and Paganoni, AM

Abstract

The relative risk of developing idiopathic PD is 1.5 times greater in men than in women, but an increased female prevalence in LRRK2-carriers has been described in the Ashkenazi Jewish population. We report an update about the frequency of major LRRK2 mutations in a large series of consecutive patients with Parkinson's disease (PD), including extensive characterization of clinical features. In particular, we investigated gender-related differences in motor and non-motor symptoms in the LRRK2 population. Methods: 2976 unrelated consecutive Italian patients with degenerative Parkinsonism were screened for mutations on exon 41 (G2019S, I2020T) and a subgroup of 1190 patients for mutations on exon 31 (R1441C/G/H). Demographic and clinical features were compared between LRRK2-carriers and non-carriers, and between male and female LRRK2 mutation carriers. Results: LRRK2 mutations were identified in 40 of 2523 PD patients (1.6%) and not in other primary parkinsonian syndromes. No major clinical differences were found between LRRK2-carriers and non-carriers. We found a novel I2020L missense variant, predicted to be pathogenic. Female gender was more common amongst carriers than non-carriers (57% vs. 40%; p=0.01), without any gender-related difference in clinical features. Family history of PD was more common in women in the whole PD group, regardless of their LRRK2 status. Conclusions: PD patients with LRRK2 mutations are more likely to be women, suggesting a stronger genetic load compared to idiopathic PD. Further studies are needed to elucidate whether there is a different effect of gender on the balance between genetic and environmental factors in the pathogenesis of PD.

Published
2014

46. PP213-SUN: Swallowing Disturbances in Parkinson’s Disease

Author

Cereda, E., primary, Klersy, C., additional, Cilia, R., additional, Canesi, M., additional, Zecchinelli, A.L., additional, Mariani, C.B., additional, Tesei, S., additional, Sacilotto, G., additional, Meucci, N., additional, Zini, M., additional, Isaias, I.U., additional, Cassani, E., additional, Goldwurm, S., additional, Barichella, M., additional, and Pezzoli, G., additional

Published
2014
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47. Novel DYT11 gene mutation in patients without dopaminergic deficit (SWEDD) screened for dystonia

Author

Cilia, R., primary, Reale, C., additional, Castagna, A., additional, Nasca, A., additional, Muzi-Falconi, M., additional, Barzaghi, C., additional, Marzegan, A., additional, Granata, M., additional, Marotta, G., additional, Sacilotto, G., additional, Vallauri, D., additional, Pezzoli, G., additional, Goldwurm, S., additional, and Garavaglia, B., additional

Published
2014
Full Text
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48. Telethon Network of Genetic Biobanks: A key service for diagnosis and research on rare diseases

Author

Filocamo, M, Baldo, C, Goldwurm, S, Renieri, A, Angelini, C, Moggio, M, Mora, M, Merla, G, Politano, L, Garavaglia, B, Casareto, L, Bricarelli, F, Gibertini, S, GIBERTINI, SARA, Filocamo, M, Baldo, C, Goldwurm, S, Renieri, A, Angelini, C, Moggio, M, Mora, M, Merla, G, Politano, L, Garavaglia, B, Casareto, L, Bricarelli, F, Gibertini, S, and GIBERTINI, SARA

Abstract

Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements betwe

Published
2013

49. Analysis of vesicular monoamine transporter 2 polymorphisms in Parkinson's disease

Author

Brighina, L, Riva, C, Bertola, F, Saracchi, E, Fermi, S, Goldwurm, S, Ferrarese, C, BRIGHINA, LAURA, RIVA, CHIARA, SARACCHI, ENRICO, FERMI, SILVIA, FERRARESE, CARLO, Brighina, L, Riva, C, Bertola, F, Saracchi, E, Fermi, S, Goldwurm, S, Ferrarese, C, BRIGHINA, LAURA, RIVA, CHIARA, SARACCHI, ENRICO, FERMI, SILVIA, and FERRARESE, CARLO

Abstract

Generation of reactive oxygen species during dopamine (DA) oxidation could be one of the factors leading to the selective loss of nigral dopaminergic neurons in Parkinson's disease (PD). Vesicular monoamine transporter type 2 (VMAT2) proteins in nerve terminals uptake dopamine into synaptic vesicles, preventing its cytoplasmic accumulation and toxic damage to nigral neurons. Polymorphisms in VMAT2 gene and in its regulatory regions might therefore serve as genetic risk factors for PD. In the present study, we have analyzed 8 single-nucleotide polymorphisms (SNPs) located within/around the VMAT2 gene for association with PD in an Italian cohort composed of 704 PD patients and 678 healthy controls. Among the 8 SNPs studied, only the 2 located within the promoter region (rs363371 and rs363324) were significantly associated with PD. In the dominant model, odds ratios were 0.72 (95% confidence interval [CI]: 0.6-0.9, p < 0.005) for rs363371 and 0.76 (95% CI: 0.6-0.9, p = 0.01) for rs363324; in the additive model, odds ratios were 0.78 (95% CI: 0.65-0.94, p = 0.008) for rs363371 and 0.85 (95% CI: 0.7-20.92, p = 0.04) for rs363324. There were no significant relationships between the remaining SNPs (rs363333, rs363399, rs363387, rs363343, rs4752045, and rs363236) and the risk of sporadic PD in any genetic model. This study adds to the previous evidence suggesting that variability in VMAT2 promoter region may confer a reduced risk of developing PD, presumably via mechanisms of gene overexpression

Published
2013

50. Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.

Author

Es, M.A. van, Schelhaas, H.J., Vught, P.W. van, Ticozzi, N., Andersen, P.M., Groen, E.J., Schulte, C., Blauw, H.M., Koppers, M., Diekstra, F.P., Fumoto, K., Leclerc, A.L., Keagle, P., Bloem, B.R., Scheffer, H., Nuenen, B.F.L. van, Blitterswijk, M. van, Rheenen, W. van, Wills, A.M., Lowe, P.P., Hu, G.F., Yu, W., Kishikawa, H., Wu, D., Folkerth, R.D., Mariani, C., Goldwurm, S., Pezzoli, G., Damme, P. van, Lemmens, R., Dahlberg, C., Birve, A., Fernandez-Santiago, R., Waibel, S., Klein, C., Weber, M., Kooi, A.J. van der, Visser, M. de, Verbaan, D., Hilten, J.J. van, Heutink, P., Hennekam, E.A., Cuppen, E., Berg, D., Brown, R.H. Jr., Silani, V., Gasser, T., Ludolph, A.C., Robberecht, W., Ophoff, R.A., Veldink, J.H., Pasterkamp, R.J., Bakker, P.I. de, Landers, J.E., Warrenburg, B.P.C. van de, Berg, L.H. van den, Es, M.A. van, Schelhaas, H.J., Vught, P.W. van, Ticozzi, N., Andersen, P.M., Groen, E.J., Schulte, C., Blauw, H.M., Koppers, M., Diekstra, F.P., Fumoto, K., Leclerc, A.L., Keagle, P., Bloem, B.R., Scheffer, H., Nuenen, B.F.L. van, Blitterswijk, M. van, Rheenen, W. van, Wills, A.M., Lowe, P.P., Hu, G.F., Yu, W., Kishikawa, H., Wu, D., Folkerth, R.D., Mariani, C., Goldwurm, S., Pezzoli, G., Damme, P. van, Lemmens, R., Dahlberg, C., Birve, A., Fernandez-Santiago, R., Waibel, S., Klein, C., Weber, M., Kooi, A.J. van der, Visser, M. de, Verbaan, D., Hilten, J.J. van, Heutink, P., Hennekam, E.A., Cuppen, E., Berg, D., Brown, R.H. Jr., Silani, V., Gasser, T., Ludolph, A.C., Robberecht, W., Ophoff, R.A., Veldink, J.H., Pasterkamp, R.J., Bakker, P.I. de, Landers, J.E., Warrenburg, B.P.C. van de, and Berg, L.H. van den

Abstract

1 december 2011, Contains fulltext : 95644.pdf (publisher's version ) (Closed access), OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 x 10(-6) for ALS and p = 4.3 x 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964-973.

Published
2011

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