Bruni Amalia C, Takahashi-Fujigasaki Junko, Maltecca Francesca, Foncin Jean Francois, Servadio Antonio, Casari Giorgio, D'Adamo Pio, Maletta Raffaele, Curcio Sabrina A M, De Michele Giuseppe, Filla Alessandro, El Hachimi Khalid H, Duyckaerts Charles
Regional Neurogenetic Center AS6, Lamezia Terme, Italy.
Arch Neurol. 2004 Aug;61(8):1314-20. doi: 10.1001/archneur.61.8.1314.
Spinocerebellar ataxia type 17 is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the TATA box-binding protein gene. Ataxia is typically the first sign whereas behavioral symptoms occur later.
To characterize the unusual phenotypic expression of a large spinocerebellar ataxia type 17 kindred.
Clinical, neuropathological, and molecular genetic characterization of a 4-generation family with 16 affected patients.
Behavioral symptoms and frontal impairment dominated the early stages preceding ataxia, rigidity, and dystonic movements. Neuropathological examination showed cortical, subcortical, and cerebellar atrophy. Purkinje cell loss and gliosis, pseudohypertrophic degeneration of the inferior olive, marked neuronal loss and gliosis in the caudate nucleus, and in the medial thalamic nuclei were salient features together with neuronal intranuclear inclusions stained with anti-TATA box-binding protein and antipolyglutamine antibodies. The disease was caused by a stable 52 CAG repeat expansion of the TATA box-binding protein gene, although there was apparent variability in the age of onset.
The characteristics of this family broaden the clinical picture of spinocerebellar ataxia type 17: initial presenile dementia with behavioral symptoms should be added to ataxia, rigidity, and dystonic movements, which are more commonly encountered.
17型脊髓小脑共济失调是一种常染色体显性遗传性小脑共济失调，由TATA盒结合蛋白基因中的CAG重复序列扩增引起。共济失调通常是首发症状，而行为症状出现较晚。
描述一个大型17型脊髓小脑共济失调家系的异常表型表达。
对一个有16名受累患者的四代家庭进行临床、神经病理学和分子遗传学特征分析。
行为症状和额叶功能障碍在共济失调、僵硬和张力障碍性运动之前的早期阶段占主导地位。神经病理学检查显示皮质、皮质下和小脑萎缩。浦肯野细胞丢失和胶质细胞增生、下橄榄核假肥大性变性、尾状核和内侧丘脑核显著的神经元丢失和胶质细胞增生，以及用抗TATA盒结合蛋白和抗多聚谷氨酰胺抗体染色的神经元核内包涵体是突出特征。该疾病由TATA盒结合蛋白基因稳定的52个CAG重复序列扩增引起，尽管发病年龄存在明显差异。
该家系的特征拓宽了17型脊髓小脑共济失调的临床谱：除了更常见的共济失调、僵硬和张力障碍性运动外，还应将伴有行为症状的早老性痴呆初期纳入其中。
