Zeman A, Stone J, Porteous M, Burns E, Barron L, Warner J
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
J Neurol Neurosurg Psychiatry. 2004 Mar;75(3):459-65. doi: 10.1136/jnnp.2003.018895.
To establish whether the DNA expansion linked to spinocerebellar ataxia type 8 (SCA 8) is associated with ataxia in Scotland; to clarify the range of associated clinical phenotypes; and to compare the findings with previous reports.
DNA was screened from 1190 anonymised controls, 137 subjects who had tested negative for Huntington's disease, 176 with schizophrenia, and 173 with undiagnosed ataxia. Five unrelated ataxic patients with the SCA 8 expansion and a sixth identified subsequently had clinical and psychometric assessment; the clinical features were available in a seventh. A systematic search for other reports of SCA 8 was undertaken.
Over 98% of SCA 8 CTA/CTG repeat lengths fell between 14 and 40. Repeat lengths over 91 were observed in three healthy controls (0.12%), two patients with suspected Huntington's disease (0.73%), and six ataxic subjects (1.74%; p<0.0005 v healthy controls). Repeat lengths over 100 occurred in five ataxic subjects but in only one control. All seven symptomatic subjects with the SCA 8 expansion had a cerebellar syndrome; four had upper motor neurone signs; and 5/6 assessed had cognitive complaints. There was personality change in two and mood disturbance in three. In published reports, SCA 8 repeat lengths over 91 occurred in approximately 0.5% of the healthy population but were over-represented among ataxic patients (3.4%; p<0.0001). The predominant clinical phenotype was cerebellar, with pyramidal signs in 50%, and neuropsychiatric features in some cases.
SCA 8 expansion is a risk factor for a cerebellar syndrome, often associated with upper motor neurone and neuropsychiatric features. The expansion occurs unexpectedly often in the general population.
确定与8型脊髓小脑共济失调（SCA 8）相关的DNA扩增在苏格兰是否与共济失调有关；阐明相关临床表型的范围；并将研究结果与先前的报告进行比较。
对1190名匿名对照、137名亨廷顿舞蹈病检测呈阴性的受试者、176名精神分裂症患者以及173名未确诊的共济失调患者的DNA进行筛查。对5名携带SCA 8扩增的无亲缘关系的共济失调患者以及随后确定的第6名患者进行了临床和心理测量评估；第7名患者的临床特征也可获取。对SCA 8的其他报告进行了系统检索。
超过98%的SCA 8 CTA/CTG重复长度在14至40之间。在3名健康对照者（0.12%）、2名疑似亨廷顿舞蹈病患者（0.73%）和6名共济失调受试者（1.74%；与健康对照相比，p<0.0005）中观察到重复长度超过91。重复长度超过100出现在5名共济失调受试者中，但仅在1名对照者中出现。所有7名携带SCA 8扩增的有症状受试者均患有小脑综合征；4名有上运动神经元体征；6名接受评估的受试者中有5名有认知主诉。2名有性格改变，3名有情绪障碍。在已发表的报告中，重复长度超过91在约0.5%的健康人群中出现，但在共济失调患者中比例过高（3.4%；p<0.000）。主要临床表型为小脑型，50%有锥体束征，部分病例有神经精神特征。
SCA 8扩增是小脑综合征的一个危险因素，常与上运动神经元和神经精神特征相关。这种扩增在普通人群中意外地经常出现。
