Mutations in progranulin explain atypical phenotypes with variants in MAPT
Mutations in progranulin explain atypical phenotypes with variants in MAPT
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DOI：
10.1093/brain/awl289
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发表时间：
2006-11-01
期刊：
影响因子：
14.5
通讯作者：
Hutton, Mike
中科院分区：
文献类型：
--
作者：
Pickering-Brown, Stuart M.;Baker, Matt;Hutton, Mike
早老蛋白-1 (PSEN1) 突变会导致常染色体显性阿尔茨海默病，而 MAPT 突变会导致与 17 号染色体相关的家族性 tau 蛋白病额颞叶痴呆 (FTDP-17)。然而，有报道称 PSEN1 和 MAPT 突变与泛素阳性 tau 阴性包涵体病理的 FTD 病例相关。在这里，我们证明 MAPT 变异几乎肯定是罕见的良性多态性，因为所有这些病例都含有颗粒体蛋白前体 (PGRN) 突变。最近显示 PGRN 突变会导致泛素阳性 FTDP-17。
Mutations in presenilin-1 (PSEN1) cause autosomal dominant Alzheimer's disease and mutations in MAPT cause the familial tauopathy Frontotemporal dementia linked to chromosome 17 (FTDP-17). However, there have been reports of mutations in PSEN1 and MAPT associated with cases of FTD with ubiquitin-positive tau-negative inclusion pathology. Here, we demonstrate that the MAPT variants are almost certainly rare benign polymorphisms as all of these cases harbour mutations in Progranulin (PGRN). Mutations in PGRN were recently shown to cause ubiquitin-positive FTDP-17.