Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau
Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau
复制标题
DOI：
10.1097/00005072-199906000-00011
复制
发表时间：
1999-06-01
影响因子：
3.2
通讯作者：
Ghetti, B
中科院分区：
文献类型：
--
作者：
Bugiani, O;Murrell, JR;Ghetti, B
tau基因已被发现是与17号染色体相关的刚性痴呆的位点。外显子和内含子突变已经在许多家族中被描述。在这里，我们描述了一个新家族中tau基因外显子10的P301S突变。这个家庭有两名成员受到影响。一个人表现为额颞叶痴呆，而他的儿子则表现为皮质基底变性，这表明相同的tau基因缺陷可导致两种不同的临床表型。两个人都在第三个十年迅速发展为进行性疾病。神经病理学上，父亲表现出广泛的丝状病理，由过度磷酸化的tau蛋白组成。从生化角度来看，P301S突变的重组tau蛋白促进微管组装的能力大大降低。
The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.