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Research paper
Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion
  1. Masato Obayashi1,
  2. Giovanni Stevanin2,3,4,5,6,
  3. Matthis Synofzik7,8,
  4. Marie-Lorraine Monin2,3,4,
  5. Charles Duyckaerts2,3,4,9,
  6. Nozomu Sato1,
  7. Nathalie Streichenberger10,
  8. Alain Vighetto11,
  9. Virginie Desestret12,13,14,
  10. Christelle Tesson2,3,4,6,
  11. H-Erich Wichmann15,16,
  12. Thomas Illig17,
  13. Johanna Huttenlocher18,
  14. Yasushi Kita19,
  15. Yuishin Izumi20,
  16. Hidehiro Mizusawa1,
  17. Ludger Schöls7,8,
  18. Thomas Klopstock21,22,23,24,
  19. Alexis Brice2,3,4,5,
  20. Kinya Ishikawa1,
  21. Alexandra Dürr2,3,4,5
  1. 1Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
  2. 2Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France
  3. 3Inserm, U1127, Paris, France
  4. 4Cnrs, UMR 7225, Paris, France
  5. 5AP-HP, Groupe Hospitalier Pitié-Salpêtriére, Departement of Genetics and Cytogenetics, Paris, France
  6. 6Ecole Pratique des Hautes Etudes, Groupe de Neurogénétique, Paris, France
  7. 7Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany
  8. 8German Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany
  9. 9Laboratoire de Neuropathologie R. Escourolle, Groupe Hospitalier Pitié-Salpêtrière, 47 Blvd de l'Hôpital, Paris, France
  10. 10Pathology and Biochemistry, Groupement Hospitalier Est, Hospices Civils de Lyon/Claude Bernard University, Lyon, France
  11. 11Neurology Department, Hôpital Pierre Wertheimer, Lyon, France
  12. 12Neurology D, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France
  13. 13Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Lyon, France
  14. 14Université de Lyon—Université Claude Bernard Lyon 1, Lyon, France
  15. 15Institute of Epidemiology I, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
  16. 16Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
  17. 17Unit for Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
  18. 18Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
  19. 19Neurology Service, Hyogo Brain and Heart Center at Himeji, Himeji, Hyogo, Japan
  20. 20Department of Clinical Neuroscience, The University of Tokushima Graduate School, Tokushima, Japan
  21. 21Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-Universität München, Munich, Germany
  22. 22German Network for Mitochondrial Disorders (mitoNET)
  23. 23DZNE—German Center for Neurodegenerative Diseases, Munich, Germany
  24. 24German Center for Vertigo and Balance Disorders, Munich, Germany
  1. Correspondence to Dr Alexis Brice, Institut du Cerveau et de la Moelle épinière, Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France; alexis.brice{at}


Objective Spinocerebellar ataxia 36 (SCA36) is an autosomal-dominant neurodegenerative disorder caused by a large (>650) hexanucleotide GGCCTG repeat expansion in the first intron of the NOP56 gene. The aim of this study is to clarify the prevalence, clinical and genetic features of SCA36.

Methods The expansion was tested in 676 unrelated SCA index cases and 727 controls from France, Germany and Japan. Clinical and neuropathological features were investigated in available family members.

Results Normal alleles ranged between 5 and 14 hexanucleotide repeats. Expansions were detected in 12 families in France (prevalence: 1.9% of all French SCAs) including one family each with Spanish, Portuguese or Chinese ancestry, in five families in Japan (1.5% of all Japanese SCAs), but were absent in German patients. All the 17 SCA36 families shared one common haplotype for a 7.5 kb pairs region flanking the expansion. While 27 individuals had typically long expansions, three affected individuals harboured small hexanucleotide expansions of 25, 30 and 31 hexanucleotide repeat-units, demonstrating that such a small expansion could cause the disease. All patients showed slowly progressive cerebellar ataxia frequently accompanied by hearing and cognitive impairments, tremor, ptosis and reduced vibration sense, with the age at onset ranging between 39 and 65 years, and clinical features were indistinguishable between individuals with short and typically long expansions. Neuropathology in a presymptomatic case disclosed that Purkinje cells and hypoglossal neurons are affected.

Conclusions SCA36 is rare with a worldwide distribution. It can be caused by a short GGCCTG expansion and associates various extracerebellar symptoms.


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