Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion.
J Neurol Neurosurg Psychiatry. 2014-12-04; 86(9): 986-995
DOI: 10.1136/jnnp-2014-309153
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1. J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):986-95. doi:
10.1136/jnnp-2014-309153. Epub 2014 Dec 4.
Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by
a short hexanucleotide GGCCTG repeat expansion.
Obayashi M(1), Stevanin G(2), Synofzik M(3), Monin ML(4), Duyckaerts C(5), Sato
N(1), Streichenberger N(6), Vighetto A(7), Desestret V(8), Tesson C(9), Wichmann
HE(10), Illig T(11), Huttenlocher J(12), Kita Y(13), Izumi Y(14), Mizusawa H(1),
Schöls L(3), Klopstock T(15), Brice A(16), Ishikawa K(1), Dürr A(16).
Author information:
(1)Department of Neurology and Neurological Sciences, Graduate School, Tokyo
Medical and Dental University, Tokyo, Japan.
(2)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.
(3)Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain
Research, Tübingen, Germany German Centre of Neurodegenerative Diseases,
University of Tübingen, Tübingen, Germany.
(4)Sorbonne Universités, Université Pierre et Marie Curie – Paris 06, UMR_S1127,
Paris, France Inserm, U1127, Paris, France Cnrs, UMR 7225, Paris, France.
(5)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.
(6)Pathology and Biochemistry, Groupement Hospitalier Est, Hospices Civils de
Lyon/Claude Bernard University, Lyon, France.
(7)Neurology Department, Hôpital Pierre Wertheimer, Lyon, France.
(8)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.
(9)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.
(10)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.
(11)Unit for Molecular Epidemiology, Helmholtz Zentrum München-German Research
Center for Environmental Health, Neuherberg, Germany.
(12)Institute of Medical Genetics and Applied Genomics, University of Tübingen,
Tübingen, Germany.
(13)Neurology Service, Hyogo Brain and Heart Center at Himeji, Himeji, Hyogo,
Japan.
(14)Department of Clinical Neuroscience, The University of Tokushima Graduate
School, Tokushima, Japan.
(15)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.
(16)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.
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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DOI: 10.1136/jnnp-2014-309153
PMID: 25476002 [Indexed for MEDLINE]