title: Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion.
abstract: 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.
authors.affiliation: Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Obayashi
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtriére, Departement of Genetics and Cytogenetics, Paris, France Ecole Pratique des Hautes Etudes, Groupe de Neurogénétique, Paris, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany German Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany.
authors.forename: Matthis
authors.initials: M
authors.lastname: Synofzik
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France.
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Monin
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France Laboratoire de Neuropathologie R. Escourolle, Groupe Hospitalier Pitié-Salpêtrière, 47 Blvd de l'Hôpital, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Sato
authors.affiliation: Pathology and Biochemistry, Groupement Hospitalier Est, Hospices Civils de Lyon/Claude Bernard University, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.affiliation: Neurology Department, Hôpital Pierre Wertheimer, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Vighetto
authors.affiliation: Neurology D, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Lyon, France Université de Lyon-Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Desestret
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France Ecole Pratique des Hautes Etudes, Groupe de Neurogénétique, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Tesson
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.affiliation: Unit for Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Huttenlocher
authors.affiliation: Neurology Service, Hyogo Brain and Heart Center at Himeji, Himeji, Hyogo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kita
authors.affiliation: Department of Clinical Neuroscience, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany German Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.affiliation: Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-Universität München, Munich, Germany German Network for Mitochondrial Disorders (mitoNET) DZNE-German Center for Neurodegenerative Diseases, Munich, Germany German Center for Vertigo and Balance Disorders, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtriére, Departement of Genetics and Cytogenetics, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kinya
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie - Paris 06, UMR_S1127, Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtriére, Departement of Genetics and Cytogenetics, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
mesh_terms: D000369:Aged, 80 and over; D000483:Alleles; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D019680:Trinucleotide Repeat Expansion
chemical_list: C486600:NOP56 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins
keywords: CEREBELLAR ATAXIA; CLINICAL NEUROLOGY; NEUROEPIDEMIOLOGY; NEUROGENETICS