caa a22 4500 397573200 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1887 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1887 Screening for Proteins with Polyglutamine Expansions in Autosomal Dominant Cerebellar Ataxias [Elektronische Daten] [Giovanni Stevanin, Yvon Trottier, Géraldine Cancel, Alexandra Dürr, Gilles David, Olivier Didierjean, Katrin Bürk, Georges Imbert, Frederic Saudou, Myriem Abada-Bendib, Isabelle Gourfinkel-An, Ali Benomar, Nacer Abbas, Thomas Klockgether, Djamel Grid, Yves Agid, Jean-Louis Mandel, Alexis Brice] Expansion of trinucleotide CAG repeats coding for polyglutamine has been implicated in five neurodegenerative disorders, including spinocerebellar ataxia (SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of type I autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody which specifically recognizes large polyglutamine tracts, particularly those that are expanded, we recently reported the detection of proteins with pathological glutamine expansions in lymphoblasts from another form of ADCA type I, SCA2, as well as from patients presenting with the distinct phenotype of ADCA type II. We now have screened a large series of patients with ADCA or isolated cases with cerebellar ataxia, for the presence of proteins with polyglutamine expansions. A 150 kDa SCA2 protein was detected in 16 out of 40 families with ADCA type I. This corresponds to 24% of all ADCA type I families, which is much more frequent than SCA1 in this series of patients (13%). The signal intensity of the SCA2 protein was negatively correlated to age at onset, as expected for an expanded and unstable trinucleotide repeat mutation. The disease segregated with markers closely linked to the SCA2 locus in all identified SCA2 families. In addition, a specific 130 kDa protein, which segregated with the disease, was detected in lymphoblasts of patients from nine families with ADCA type II. It was also visualized in the cerebral cortex of one of the patients, demonstrating its translation in the nervous system. Finally, no new disease-related proteins containing expanded polyglutamine tracts could be detected in lymphoblasts from the remaining patients with ADCA or isolated cases with cerebellar ataxia. © 1993 Oxford University Press Stevanin Giovanni INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Trottier Yvon Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut Cancel Géraldine INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Dürr Alexandra INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut David Gilles INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Didierjean Olivier INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Bürk Katrin Department of Neurology, University of Tübingen, Tübingen, Germany aut Imbert Georges Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut Saudou Frederic Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut Abada-Bendib Myriem INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Gourfinkel-An Isabelle INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Benomar Ali Service de Neurologie, Hôpital des Spécialités, Rabat, Morocco aut Abbas Nacer INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Klockgether Thomas Department of Neurology, University of Tübingen, Tübingen, Germany aut Grid Djamel Service de Neurologie, CHU Mustapha, Algiers, Algeria aut Agid Yves INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Mandel Jean-Louis Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut Brice Alexis INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1887-1892 0964-6906 5:12<1887 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1887 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1887 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stevanin Giovanni INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Trottier Yvon Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut NATIONALLICENCE 700 1- Cancel Géraldine INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Dürr Alexandra INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- David Gilles INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Didierjean Olivier INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Bürk Katrin Department of Neurology, University of Tübingen, Tübingen, Germany aut NATIONALLICENCE 700 1- Imbert Georges Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut NATIONALLICENCE 700 1- Saudou Frederic Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut NATIONALLICENCE 700 1- Abada-Bendib Myriem INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Gourfinkel-An Isabelle INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Benomar Ali Service de Neurologie, Hôpital des Spécialités, Rabat, Morocco aut NATIONALLICENCE 700 1- Abbas Nacer INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Klockgether Thomas Department of Neurology, University of Tübingen, Tübingen, Germany aut NATIONALLICENCE 700 1- Grid Djamel Service de Neurologie, CHU Mustapha, Algiers, Algeria aut NATIONALLICENCE 700 1- Agid Yves INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 700 1- Mandel Jean-Louis Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, CU de Strasbourg, France aut NATIONALLICENCE 700 1- Brice Alexis INSERM U289 and Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1887-1892 0964-6906 5:12<1887 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford