Atypical presentation of a novel Presenilin 1 R377W mutation: sporadic, late-onset Alzheimer disease with epilepsy and frontotemporal atrophy
Atypical presentation of a novel Presenilin 1 R377W mutation: sporadic, late-onset Alzheimer disease with epilepsy and frontotemporal atrophy
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DOI：
10.1007/s10072-011-0714-1
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发表时间：
2012-04-01
影响因子：
3.3
通讯作者：
Padovani, Alessandro
中科院分区：
文献类型：
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作者：
Borroni, Barbara;Pilotto, Andrea;Padovani, Alessandro
早老素 1 (PSEN1) 内的突变是单基因阿尔茨海默病 (AD) 的最常见原因。即使经常发生具有常染色体显性遗传模式并表现出记忆缺陷的早发性疾病，临床表型也存在很大差异。在目前的工作中，我们描述了一名迟发性 AD 患者的病例，该患者没有任何痴呆症阳性家族史，且与癫痫发作和行为症状相关。结构和功能神经影像显示额颞部变化，无后双顶脑异常。脑脊液分析与 AD 模式一致，A beta 42 减少，Tau 和磷酸-Tau 增加。在外显子 8 内检测到 PSEN1 基因内的新致病突变，导致精氨酸替换为色氨酸 (AGG > TGG: R377W)，影响剪接连接和蛋白质功能。本文报道的病例进一步证实了 PSEN1 突变的异质性，以及在非典型表现病例中考虑基因筛查的必要性。
Mutations within Presenilin 1 (PSEN1) represent the most common cause of monogenic Alzheimer Disease (AD). The clinical phenotype is highly variable, even if early onset disease with an autosomal dominant pattern of inheritance and presenting memory deficits usually occur. In the present work, we described the case of a late-onset AD patient, without any positive family history for dementia, and associated with seizures and behavioural symptoms. Structural and functional neuroimaging showed frontotemporal changes without posterior biparietal brain abnormalities. Cerebrospinal analysis was consistent with AD pattern, with decreased A beta 42 and increased Tau and phospho-Tau. A novel pathogenetic mutation within PSEN1 gene was detected within exon 8, leading to a substitution from arginine to tryptophan (AGG > TGG: R377W), affecting a splice junction and protein function. The case herein reported further confirms the heterogeneity of PSEN1 mutations and the need to take into account genetic screening in those cases with atypical presentation.