Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
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.
J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):986-95. doi: 10.1136/jnnp-2014-309153. Epub 2014 Dec 4.
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.
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.
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.
SCA36 is rare with a worldwide distribution. It can be caused by a short GGCCTG expansion and associates various extracerebellar symptoms.
脊髓小脑性共济失调 36 型（SCA36）是一种常染色体显性遗传性神经退行性疾病，由 NOP56 基因第一内含子中 GGCCTG 六核苷酸重复扩增引起，重复序列大于 650 个。本研究旨在阐明 SCA36 的患病率、临床和遗传特征。
在来自法国、德国和日本的 676 名无关 SCA 索引病例和 727 名对照中检测了扩增情况。对可获得家族成员的临床和神经病理学特征进行了研究。
正常等位基因的重复次数在 5 到 14 个六核苷酸之间。在法国的 12 个家族中发现了扩增（所有法国 SCA 的患病率为 1.9%），其中包括一个具有西班牙、葡萄牙或中国血统的家族，在日本的 5 个家族中发现了扩增（所有日本 SCA 的患病率为 1.5%），但在德国患者中未发现扩增。所有 17 个 SCA36 家系均共享一个围绕扩增的 7.5kb 对侧翼的共同单倍型。虽然 27 名个体具有典型的长扩增，但 3 名受影响的个体具有 25、30 和 31 个六核苷酸重复单位的小六核苷酸扩增，表明如此小的扩增也可能导致疾病。所有患者均表现出进行性缓慢的小脑共济失调，常伴有听力和认知障碍、震颤、上睑下垂和振动觉减退，发病年龄在 39 至 65 岁之间，短扩增和典型长扩增个体的临床特征无明显差异。在一个无症状病例的神经病理学检查中发现，浦肯野细胞和舌下神经核受影响。
SCA36 发病率低，分布广泛。它可以由短的 GGCCTG 扩增引起，并伴有各种小脑外症状。
