Divergent clinical and neuropathological phenotype in a Gerstmann-Straussler-Scheinker P102L family
Divergent clinical and neuropathological phenotype in a Gerstmann-Straussler-Scheinker P102L family
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DOI：
10.1111/j.1600-0404.2011.01628.x
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Alafuzoff, I.
中科院分区：
文献类型：
--
作者：
Popova, S. N.;Tarvainen, I.;Alafuzoff, I.
目的 Gerstmann-Straussler-Scheinker 综合征属于与朊病毒蛋白基因（PRNP）突变相关的遗传性朊病毒疾病。最常见的是密码子 102 处的点突变，导致脯氨酸被亮氨酸取代 (P102L)。先前的报告表明具有这种突变的个体之间存在表型异质性。在这里，我们描述了第一个具有 PNRP 基因 P102L 突变的芬兰亲属成员的临床和病理表型。材料和方法 我们对一个家庭的五个成员进行了遗传和临床信息，并对其中三个死后大脑进行了系统的组织学和免疫组织化学评估。结果患者之间的临床表现、病程和临床表型（共济失调与痴呆）各不相同。临床症状与朊病毒蛋白免疫反应性聚集体的神经解剖学分布之间存在显着相关性，即共济失调中的幕下优势与痴呆中的皮质优势。在一名以痴呆为发病症状的患者的大脑中观察到了与阿尔茨海默病相关的显着病理学。结论 这是第一个携带 PRNP 基因 P102L 突变的斯堪的纳维亚家庭。当治疗共济失调和/或病因不明的痴呆患者时，鉴别诊断中应考虑 Gerstmann-Straussler-Scheinker 综合征。
Objectives Gerstmann-Straussler-Scheinker syndrome belongs to the genetic prion diseases being associated with mutations in the prion protein gene (PRNP). The most common is the point mutation at codon 102, leading to the substitution of proline to leucine (P102L). Previous reports have indicated a phenotypic heterogeneity among individuals with this mutation. Here, we describe the clinical and pathological phenotype in members of the first Finnish kindred with the P102L mutation in the PNRP gene. Materials and Methods Genetic and clinical information was available in five members of a family, while a systematic histologic and immunohistochemical assessment of the post-mortem brain was carried out in three. Results Clinical presentation, disease duration and the clinical phenotype (ataxia vs dementia) varied between patients. There was a significant correlation between clinical symptoms and the neuroanatomical distribution of prion protein-immunoreactive aggregates, i.e. subtentorial predominance in ataxia vs cortical predominance in dementia. A significant concomitant Alzheimer is disease-related pathology was observed in the brain of one patient with dementia as onset symptom. Conclusions This is the first Scandinavian family carrying the P102L mutation in the PRNP gene. Gerstmann-Straussler-Scheinker syndrome should be considered in the differential diagnosis when handling with patients with ataxia and/or dementia of unclear aetiology.