PSEN1 G417S mutation in a Chinese pedigree causing early-onset parkinsonism with cognitive impairment
PSEN1 G417S mutation in a Chinese pedigree causing early-onset parkinsonism with cognitive impairment
复制标题
中国家系PSEN1 G417S突变导致早发性帕金森病伴认知障碍
DOI：
10.1016/j.neurobiolaging.2022.03.016
复制
发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Jifeng Guo
中科院分区：
文献类型：
--
作者：
Li Jiang;Yan Qin;Yu-Wen Zhao;Qian Zeng;Hong-Xu Pan;Zhenhua Liu;Qi-Ying Sun;Qian Xu;Jie-Qiong Tan;Xin-Xiang Yan;Jin-Chen Li;Bei-Sha Tang;Jifeng Guo
早老素1（PSEN1）突变是家族性阿尔茨海默病的主要病因。在日本，致病性变异PSEN1 p.G417S据报道与痉挛性截瘫和棉絮状斑块有关。在此，我们报告一个中国的三代家系，其中10名患者在30或40岁时出现早发性且进展迅速的帕金森综合征并伴有认知障碍。另外3名在世患者出现不同程度的认知障碍，但无运动障碍。脑部磁共振成像显示白质高信号、多发微出血以及血管周围间隙扩大。对先证者进行全外显子组测序分析，检测到PSEN1基因的p.G417S突变，通过桑格测序发现该突变在家族内与疾病表型完全共分离。三维蛋白质结构预测该突变可能影响与脂质膜的接触以及与β - 连环蛋白的相互作用。我们的研究为PSEN1基因突变相关的临床表现和影像学的异质性提供了见解。
Presenilin 1 (PSEN1) mutations are a major cause of familial Alzheimer's disease. The pathogenic variant, PSEN1 p.G417S, has been reported to be associated with spastic paraparesis and cotton wool plaques in Japan. Here, we report a 3 generation Chinese pedigree that included 10 patients presenting with early-onset and rapid progression of parkinsonism with cognitive impairment in their third or fourth decade of life. Three additional living patients developed different degrees of cognitive impairment, without movement disorders. Magnetic resonance imaging of the brain showed white matter hyperintensities, multiple microbleeds, and enlarged perivascular spaces. Whole exome sequencing analysis of the proband detected the mutation, p.G417S, in PSEN1, which was completely co-segregated with the disease phenotype within the family by Sanger sequencing. 3D protein structures predicted that the mutation might influence contact with the lipid membrane and the interaction with beta-catenin. Our study provides insights into the heterogeneity in clinical presentation and imaging associated with mutations in PSEN1.
登录
查看更多内容
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
DOI：
10.1017/9781108587921.004
发表时间：
2008-11
期刊：
Language in Dementia
影响因子：
--
作者：
Li Qiang
通讯作者：
Li Qiang
影响因子：
2.8
作者：
Horst Urbach
通讯作者：
Horst Urbach
帕金森氏病的遗传结构。
DOI：
10.1016/s1474-4422(19)30287-x
发表时间：
2020-02
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Blauwendraat C;Nalls MA;Singleton AB
通讯作者：
Singleton AB
影响因子：
64.8
作者：
Zhang, ZH;Hartmann, H;Yankner, BA
通讯作者：
Yankner, BA