早老素1基因P．G378E突变导致的早发家族性阿尔茨海默病一家系

A Chinese pedigree with early-onset familial Alzheimer＇s disease caused by presenilin 1 p. G378E mutation

目的探讨一个早发家族性阿尔茨海默病（EO-FAD）家系的临床表现及存在的基因突变。方法对先证者及其家系成员进行了体格检查、头颅MRI检查和基因检测，并在先证者死亡后对其进行了尸检。结果该家系中有15名成员出现早老素1基因（PSENl）P.G378E突变，9名成员已经出现EO-FAD相关临床或影像学表现。先证者尸检组织病理学结果显示脑萎缩明显，尤以额叶和颞叶最为显著；HE染色和免疫组织化学染色结果显示额、颞及枕叶皮质等部位出现神经元丢失、胶质细胞增生，大脑皮质可见老年斑以及神经原纤维缠结。先证者妹妹出现和其类似的临床和影像学表现，而家系内其他患者目前仅出现记忆力进行性减退。结论该EO-FAD家系PSENl基因发生P.G378E突变，证实在中国人群存在这一突变现象并且导致发病。

Objective To investigate the phenotypes and genetics of an early-onset familial Alzheimer＇s disease （EO-FAD） family. Methods The clinical manifestations, brain MRI results and neuropathological findings of the proband and pedigree members of the EO-FAD family were evaluated. Autopsy was performed in the proband. Results Fifteen members of this family had a presenilin 1 （ PSEN1 ） p. G378E mutation and nine of them had clinical manifestations or the MRI changes of EO-FAD. Neuropathological findings from autopsy of the proband disclosed moderate cortical atrophy throughout the brain, especially in frontal lobe and temporal lobe. Neuronal loss with gliosis was observed in the cortices of the frontal, temporal and occipital lobes, as well as in parahippocampal gyrus. Numerous senile plaques and neurofibrillary tangles were present in the cerebral cortex. The proband＇s younger sister showed similar clinical presentations and MRI changes, and other members of this family demonstrated progressive memory loss. Conclusion A p. G378E mutation in the PSEN1 gene was identified in a Chinese EO-FAD pedigree.