Juvonen V, Hietala M, Päivärinta M, Rantamäki M, Hakamies L, Kaakkola S, Vierimaa O, Penttinen M, Savontaus M L
Department of Medical Genetics, University of Turku, Finland.
Ann Neurol. 2000 Sep;48(3):354-61.
Spinocerebellar ataxia 8 (SCA8) is caused by a CTG repeat expansion in an untranslated region of a recently cloned gene on 13q21. The pathogenic role of this trinucleotide repeat was evaluated by examining 154 Finnish ataxia patients and 448 controls. Expansions ranging from 100 to 675 repeats were present in 9 (6%) unrelated patients and in 13 (3%) controls. There was a threefold excess of shorter expansions (<204 repeats) in the ataxia series, and the expansions tended to cluster in patients with a family history for the disease. Clinical and genetic data were subsequently collected from 15 patients. Common initial symptoms included gait instability, dysarthria, and tremor. A marked cerebellar atrophy in magnetic resonance imaging or computed tomography was found in all patients. Pyramidal affection was often seen, and various kinds of cognitive impairment were evident in 40% of patients. Disease progression was slow, and fluctuation of symptoms was commonly observed. A maternal penetrance bias was not seen, nor was there any clear-cut negative correlation between age of onset and repeat number. Meiotic but not mitotic instability of the repeat expansion was evident. Haplotype analysis suggests multiple origins for the Finnish spinocerebellar ataxia 8 repeat expansions.
脊髓小脑共济失调8型（SCA8）是由位于13q21的一个最近克隆基因的非翻译区的CTG重复序列扩增引起的。通过检查154名芬兰共济失调患者和448名对照，评估了这种三核苷酸重复序列的致病作用。100至675次重复的扩增存在于9名（6%）无亲缘关系的患者和13名（3%）对照中。共济失调组中较短扩增（<204次重复）的比例是对照组的三倍，并且扩增倾向于聚集在有该疾病家族史的患者中。随后收集了15名患者的临床和遗传数据。常见的初始症状包括步态不稳、构音障碍和震颤。所有患者在磁共振成像或计算机断层扫描中均发现明显的小脑萎缩。常可见锥体束受累，40%的患者有明显的各种认知障碍。疾病进展缓慢，症状波动常见。未发现母系遗传偏向，发病年龄与重复次数之间也没有明显的负相关。重复序列扩增存在减数分裂而非有丝分裂不稳定性。单倍型分析表明芬兰脊髓小脑共济失调8型重复序列扩增有多个起源。
