GERSTMANN-STRAUSSLER-SCHEINKER DISEASE AND THE INDIANA KINDRED
GERSTMANN-STRAUSSLER-SCHEINKER DISEASE AND THE INDIANA KINDRED
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DOI：
10.1111/j.1750-3639.1995.tb00578.x
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发表时间：
1995-01-01
期刊：
影响因子：
6.4
通讯作者：
TAGLIAVINI, F
中科院分区：
文献类型：
--
作者：
GHETTI, B;DLOUHY, SR;TAGLIAVINI, F
Gerstmann-Straussler-Scheinker病是一种常染色体显性遗传疾病，具有广泛的临床表现，包括共济失调、痉挛性轻瘫、锥体外系体征和痴呆。患者在生命的第三至第六个十年出现症状，平均患病时间为五年。朊病毒蛋白基因开放阅读框密码子102、105、117、145、198和217处的突变与GSS疾病相关。作为突变的结果，在朊病毒蛋白的相应残基处发生取代，或者如在密码子145处的终止突变的情况下，产生截短的蛋白质。神经病理学上，共同点是大脑朊蛋白淀粉样变性;然而，在已报道的家族中，中枢神经系统区域的淀粉样蛋白沉积模式存在显著差异。在密码子102突变的患者中，淀粉样变性与严重的海绵状变性共存，在密码子145、198和217突变的患者中，淀粉样变性与神经退行性变共存。在接种了受影响受试者的脑组织的动物中发生传染性海绵状脑病，其密码子102处发生突变，这表明在某些形式的遗传确定的Gerstmann-Straussler-Scheinker病中。特别是那些特征为严重的海绵状变性、淀粉样蛋白生成和感染性“因子”产生的疾病，通过仅部分了解的机制同时发生。
Gerstmann-Straussler-Scheinker disease is an autosomal dominant disorder with a wide spectrum of clinical presentations including ataxia, spastic paraparesis, extrapyramidal signs, and dementia. The patients present with symptoms in the third to sixth decade of life and the mean duration of illness is five years. Mutations at codons 102, 105, 117, 145, 198 and 217 of the open reading frame of the prion protein gene have been associated with GSS disease. As a result of the mutations, a substitution at the corresponding residues of the prion protein occurs, or as in the case of the STOP mutation at codon 145, a truncated protein is produced. Neuropathologically, the common denominator is a cerebral prion protein amyloidosis; however, there is significant variability in the pattern of amyloid deposition in regions of the central nervous system among reported families. Amyloidosis coexists with severe spongiform degeneration in patients with the mutation at codon 102, and with neurofibrillary degeneration in the patients with mutation at codons 145, 198 and 217. The development of a transmissible spongiform encephalopathy in animals inoculated with brain tissue from affected subjects with mutation at codon 102 suggests that in some forms of genetically-determined Gerstmann-Straussler-Scheinker disease. and particularly those characterized by severe spongiosis, amyloidogenesis and production of an infectious ''agent'' occur concomitantly via mechanisms that are only partially understood.