THE ORIGINAL GERSTMANN-STRAUSSLER-SCHEINKER FAMILY OF AUSTRIA - DIVERGENT CLINICOPATHOLOGICAL PHENOTYPES BUT CONSTANT PRP GENOTYPE
THE ORIGINAL GERSTMANN-STRAUSSLER-SCHEINKER FAMILY OF AUSTRIA - DIVERGENT CLINICOPATHOLOGICAL PHENOTYPES BUT CONSTANT PRP GENOTYPE
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DOI：
10.1111/j.1750-3639.1995.tb00596.x
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发表时间：
1995-07-01
期刊：
影响因子：
6.4
通讯作者：
BUDKA, H
中科院分区：
文献类型：
--
作者：
HAINFELLNER, JA;BRANTNERINTHALER, S;BUDKA, H
我们提出了新的数据与Gerstmann-Straussler-Scheinker病（GSS），目前包括221名成员在9代的原始奥地利亲属。遗传方式为常染色体显性遗传。主要临床特征是缓慢进行性共济失调和晚期高级脑功能损害。与此相反，最近的情况下，证明P102 L突变的PRNP基因有迅速发展的痴呆和严重的皮质损伤，难以区分的临床病理表型的克雅氏病（CJD）。PRNP密码子129在历史和最近的情况下都是纯合的甲硫氨酸。神经病理学证实了不同程度的海绵状变性和大量蛋白酶抗性/朊蛋白（PrP）淀粉样斑块分散在大部分大脑中作为该家族的恒定特征。一些淀粉样蛋白沉积物被营养不良的神经突包围，伴有磷酸化神经丝和异常细胞器的积聚，使人联想到阿尔茨海默型斑块。严重的端脑损伤和突触型细颗粒免疫反应性层状分布在皮质抗-PrP水合高压灭菌后的部分只在最近的病人。总之，除了密码子102和129处的PRNP基因型外，其他因素必须在确定这种遗传性脑淀粉样变性的临床病理特征中发挥作用。
We present new data on the original Austrian kindred with Gerstmann-Straussler-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.