Hainfellner J A, Brantner-Inthaler S, Cervenáková L, Brown P, Kitamoto T, Tateishi J, Diringer H, Liberski P P, Regele H, Feucht M
Institute of Neurology, University of Vienna, Austria.
Brain Pathol. 1995 Jul;5(3):201-11. doi: 10.1111/j.1750-3639.1995.tb00596.x.
We present new data on the original Austrian kindred with Gerstmann-Sträussler-Scheinker disease (GSS) which encompasses currently 221 members in 9 generations. The mode of inheritance is autosomal dominant. Predominant clinical features are slowly progressive ataxia and late impairment of higher cerebral functions. In contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly developing dementia and severe cortical damage indistinguishable from the clinicopathological phenotype of Creutzfeldt-Jakob disease (CJD). PRNP codon 129 was homozygous for methionine in both the historic and recent cases. Neuropathology confirms spongiosis of variable degree and numerous protease resistant/prion protein (PrP) amyloid plaques scattered throughout most of the brain as constant features in this family. Some amyloid deposits are surrounded by dystrophic neurites with accumulation of phosphorylated neurofilaments and abnormal organelles, reminiscent of Alzheimer-type plaques. Severe telencephalic damage and a synaptic-type fine granular immunoreactivity in laminar distribution in the cortex with anti-PrP after hydrated autoclaving of sections were seen only in the recent patient. In conclusion, factors in addition to the PRNP genotype at codons 102 and 129 must play a role in determining clinicopathological characteristics of this inherited brain amyloidosis.
我们展示了关于最初的奥地利格斯综合征（GSS）家族的新数据，该家族目前有9代共221名成员。遗传方式为常染色体显性遗传。主要临床特征为缓慢进展的共济失调和晚期高级脑功能损害。相比之下，最近一例经证实PRNP基因存在P102L突变的病例出现了快速进展的痴呆和严重的皮质损伤，其临床病理表型与克雅氏病（CJD）难以区分。在历史病例和最近的病例中，PRNP密码子129均为甲硫氨酸纯合子。神经病理学证实，该家族的恒定特征是不同程度的海绵状变性以及遍布大脑大部分区域的大量抗蛋白酶/朊蛋白（PrP）淀粉样斑块。一些淀粉样沉积物被营养不良性神经突包围，伴有磷酸化神经丝和异常细胞器的积累，类似于阿尔茨海默型斑块。仅在最近的患者中观察到严重的端脑损伤以及切片经高压灭菌水化处理后，皮质中出现的层状分布的突触型细颗粒免疫反应性。总之，除了密码子102和129处的PRNP基因型外，其他因素必定在决定这种遗传性脑淀粉样变性的临床病理特征中发挥作用。
