Rüb U, Brunt E R, Gierga K, Seidel K, Schultz C, Schöls L, Auburger G, Heinsen H, Ippel P F, Glimmerveen W F, Wittebol-Post D, Arai K, Deller T, de Vos R A I
Institute for Clinical Neuroanatomy, J.W. Goethe University, Frankfurt/Main, Germany.
Brain Pathol. 2005 Oct;15(4):287-95. doi: 10.1111/j.1750-3639.2005.tb00113.x.
Spinocerebellar ataxia type 7 (SCA7) represents a very rare and severe autosomal dominantly inherited cerebellar ataxia (ADCA). It belongs to the group of CAG-repeat or polyglutamine diseases with its underlying molecular genetical defect on chromosome 3p12-p21.1. Here, we performed a systematic study of the neuropathology on unconventional thick serial sections of the first available brain tissue of a genetically confirmed late-onset SCA7 patient with a very short CAG-repeat expansion. Along with myelin pallor of a variety of central nervous fiber tracts, we observed i) neurodegeneration in select areas of the cerebral cortex, and ii) widespread nerve cell loss in the cerebellum, thalamus, nuclei of the basal ganglia, and brainstem. In addition, upon immunocytochemical analysis using the anti-polyglutamine antibody 1C2, immunopositive neuronal intranuclear inclusions bodies (NI) were observed in all cerebellar regions, in all parts of the cerebral cortex, and in telencephalic and brainstem nuclei, irrespective of whether they underwent neurodegeneration. These novel findings provide explanations for a variety of clinical symptoms and paraclinical findings of both our and other SCA7 patients. Finally, our immunocytochemical analysis confirms previous studies which described the presence of NI in obviously degenerated brain and retinal regions as well as in apparently well-preserved brain regions and retina of SCA7 patients.
7型脊髓小脑共济失调（SCA7）是一种非常罕见且严重的常染色体显性遗传性小脑共济失调（ADCA）。它属于CAG重复或多聚谷氨酰胺疾病组，其潜在的分子遗传学缺陷位于3号染色体p12 - p21.1区域。在此，我们对一名基因确诊的晚发性SCA7患者的首个可用脑组织进行了非常规厚连续切片的神经病理学系统研究，该患者的CAG重复扩展非常短。除了多种中枢神经纤维束的髓鞘苍白外，我们还观察到：i）大脑皮质某些区域的神经变性，以及ii）小脑、丘脑、基底神经节核和脑干广泛的神经细胞丢失。此外，使用抗多聚谷氨酰胺抗体1C2进行免疫细胞化学分析时，在所有小脑区域、大脑皮质的所有部位以及端脑和脑干核中均观察到免疫阳性的神经元核内包涵体（NI），无论它们是否发生神经变性。这些新发现为我们及其他SCA7患者的各种临床症状和副临床发现提供了解释。最后，我们的免疫细胞化学分析证实了先前的研究，这些研究描述了在SCA7患者明显退化的脑和视网膜区域以及明显保存完好的脑区域和视网膜中存在NI。
