A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease.
A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease.
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DOI：
10.3233/jad-131340
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Velinov M
中科院分区：
文献类型：
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作者：
Dolzhanskaya N;Gonzalez MA;Sperziani F;Stefl S;Messing J;Wen GY;Alexov E;Zuchner S;Velinov M
对一个疑似显性库夫斯病的家族进行全外显子组测序，在三个兄弟中发现了一种新的早老素1突变p.Leu(381)Phe，这三个兄弟和他们的父亲在30岁出头时患上了进行性痴呆和运动障碍。所有受影响亲属的疾病进展异常迅速（从发病到死亡平均3.6年）。与常见的早老素1突变p.Glu(280)Ala相比，突变p.Leu(381)Phe的计算机分析预测了更多的有害影响。先证患者外周血成纤维细胞电镜检查显示库夫斯病典型的溶酶体包涵体。然而，他的大脑解剖显示了阿尔茨海默病的典型变化。
Whole exome sequencing in a family with suspected dominant Kufs disease identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who, along with their father, developed progressive dementia and motor deficits in their early 30s. All affected relatives had unusually rapid disease progression (on average 3.6 years from disease onset to death). In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease. However his brain autopsy demonstrated typical changes of Alzheimer disease.