RT Journal Article
SR Electronic
T1 Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 986
OP 995
DO 10.1136/jnnp-2014-309153
VO 86
IS 9
A1 Masato Obayashi
A1 Giovanni Stevanin
A1 Matthis Synofzik
A1 Marie-Lorraine Monin
A1 Charles Duyckaerts
A1 Nozomu Sato
A1 Nathalie Streichenberger
A1 Alain Vighetto
A1 Virginie Desestret
A1 Christelle Tesson
A1 H-Erich Wichmann
A1 Thomas Illig
A1 Johanna Huttenlocher
A1 Yasushi Kita
A1 Yuishin Izumi
A1 Hidehiro Mizusawa
A1 Ludger Schöls
A1 Thomas Klopstock
A1 Alexis Brice
A1 Kinya Ishikawa
A1 Alexandra Dürr
YR 2015
UL http://jnnp.bmj.com/content/86/9/986.abstract
AB 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.