• Masato Obayashi, Giovanni Stevanin, Matthis Synofzik, Marie-Lorraine Monin, Charles Duyckaerts, Nozomu Sato, Nathalie Streichenberger, Alain Vighetto, Virginie Desestret, Christelle Tesson, H-Erich Wichmann, Thomas Illig, Johanna Huttenlocher, Yasushi Kita, Yuishin Izumi, Hidehiro Mizusawa, Ludger Schöls, Thomas Klopstock, Alexis Brice, Kinya Ishikawa, and Alexandra Dürr.
• Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
• J. Neurol. Neurosurg. Psychiatr. 2015 Sep 1; 86 (9): 986-95.

ObjectiveSpinocerebellar 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.MethodsThe 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.ResultsNormal 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.ConclusionsSCA36 is rare with a worldwide distribution. It can be caused by a short GGCCTG expansion and associates various extracerebellar symptoms.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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