Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer's Disease with De Novo PSEN1 Mutation
Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer's Disease with De Novo PSEN1 Mutation
复制标题
阴性家族史早发性痴呆的诊断方法：PSEN1 新突变早发性阿尔茨海默病两例的启示
DOI：
10.3233/jad-181108
复制
发表时间：
2019-01-01
影响因子：
4
通讯作者：
Gauthier, Serge
中科院分区：
文献类型：
--
作者：
Liu, Jia;Wang, Qianqian;Gauthier, Serge
对于家族史不明确的早发性阿尔茨海默病（EOAD）病例，大多数病例是散发性的。有些病例的基因检测呈阳性，即不完全外显或新生突变。我们的目标是关注具有新生突变的 EOAD 病例。进行了病例报告和文献综述。开发了具有阴性家族史的早发性痴呆诊断方法的意义。我们报告了两例具有新发突变的中国 EOAD 病例。 PSEN1 G206S 基因型似乎与具有纯粹认知问题的 EOAD 表型相关。第二例患者存在 PSEN1 M233V 突变，发病年龄较早，为 25 岁，患有认知能力下降、帕金森症和癫痫。尽管由新突变引起的 EOAD 并不常见，但对于具有进行性认知衰退表型且 PET 或 CSF 分析显示淀粉样蛋白阳性的患者，应予以考虑。
For early-onset Alzheimer's disease (EOAD) cases with unclear family history, most cases are sporadic. Some cases are positive in genetic findings, that is, either incomplete penetrance or de novo mutation. We aimed to focus on EOAD cases with de novo mutations. Case reports and literature review were performed. The implication for diagnostic approach of early-onset dementia with negative family history was developed. We reported two Chinese EOAD cases with de novo mutations. The genotype PSEN1 G206S appeared to correlate with the phenotype of EOAD with pure cognitive problems. The second case had a PSEN1 M233V mutation with an earlier age of onset of 25 with cognitive decline, parkinsonism, and epilepsy. Although EOAD due to de novo mutations is not common, it should be considered in patients with a phenotype of progressive cognitive decline and amyloid positivity on PET or CSF analysis.