Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, People's Republic of China.
Laboratory of Medical Genetics, Central South University, Changsha, 410008, Hunan, People's Republic of China.
J Neurol. 2019 Dec;266(12):2979-2986. doi: 10.1007/s00415-019-09519-2. Epub 2019 Aug 30.
Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by CTA/CTG repeat expansion in the ATXN8/ATXN8OS gene.
To analyze the frequency and clinical characteristics of SCA8 patients in mainland China, we combined polymerase chain reaction (PCR) and triplet repeat-primed PCR (TRP-PCR) to detect the CTA/CTG expansion. We studied a cohort of 362 ataxia patients in which the other known causative genes had been previously excluded, from among 1294 index patients. Positive samples were validated by southern blotting.
The CTA/CTG expansion was observed in six probands, accounting for approximately 0.46% (6/1294) in all patients, and 1.66% (6/362) in patients without definite molecular diagnosis. Clinically, aside from the typical SCA8 phenotype, some patients carrying the CTA/CTG expansion exhibited the cerebellar form of multisystem atrophy (MSA-C) and ataxia with paroxysmal kinesigenic dyskinesia (PKD).
For the first time, we described the PKD phenotype in association with CTA/CTG expansion, suggesting that CTA/CTG expansion might play a role in the pathogenesis of paroxysmal dyskinesia symptoms.
脊髓小脑性共济失调 8 型（SCA8）是一种罕见的常染色体显性神经退行性疾病，由 ATXN8/ATXN8OS 基因中的 CTA/CTG 重复扩展引起。
为了分析中国大陆 SCA8 患者的频率和临床特征，我们结合聚合酶链反应（PCR）和三核苷酸重复引物 PCR（TRP-PCR）来检测 CTA/CTG 扩展。我们研究了一个由 1294 名索引患者中先前排除了其他已知致病基因的 362 名共济失调患者组成的队列。阳性样本通过Southern 印迹进行验证。
在六个先证者中观察到 CTA/CTG 扩展，占所有患者的约 0.46%（6/1294），在无明确分子诊断的患者中占 1.66%（6/362）。临床上，除了典型的 SCA8 表型外，一些携带 CTA/CTG 扩展的患者表现出小脑多系统萎缩（MSA-C）和伴有阵发性运动诱发性运动障碍（PKD）的共济失调。
我们首次描述了与 CTA/CTG 扩展相关的 PKD 表型，提示 CTA/CTG 扩展可能在阵发性运动障碍症状的发病机制中起作用。
