Department of Neurology, Azienda Universitaria-Ospedaliera of Cagliari and University of Cagliari, Sst 554, 09042, Cagliari, Monserrato, Italy,
J Neurol. 2015 Feb;262(2):375-84. doi: 10.1007/s00415-014-7575-5. Epub 2014 Nov 20.
It has been shown that different genes could be associated with distinctive clinical and radiological phenotypes of FTD. TARDBP gene has been described worldwide in few cases of FTD so its phenotype is still unclear. The objective is to study the clinical and radiological characteristics of TARDBP-related FTD. In the present study, we report clinical, neuropsychological and radiological features of five new Sardinian non-related cases of FTD carriers of the p.A382T TARDBP mutation. Furthermore, we reviewed non-related FTD cases with TARDBP mutations previously described in literature. The p.A382T missense mutation of TARDBP was present in the 21.7 % of familial cases of our FTD cohort (5/23) and in no one of the sporadic patients. 3 of 5 patients showed a temporal variant FTD and 4/5 a predominant temporal involvement at MRI. The review of the literature of FTD cases with TARDBP mutations showed that in 5 of 16 cases, the clinical phenotype was consistent with temporal variant of FTD or semantic dementia (31 %) and in 7 of 16 cases neuroimaging showed predominant temporal lobe involvement (43.7 %). Our study further supports the pathogenetic role of TARDBP mutations in pure FTD and in the full spectrum of FTD/ALS. The presence of a predominant temporal lobe involvement in a high percentage of FTD mutated patients with a peculiar clinical pattern could be useful in the differential diagnosis with other forms of dementia/FTD both sporadic and familial.
已经表明，不同的基因可能与 FTD 的独特临床和影像学表型有关。TARDBP 基因在全球少数 FTD 病例中被描述，因此其表型仍不清楚。目的是研究 TARDBP 相关 FTD 的临床和影像学特征。在本研究中，我们报告了 5 例新的撒丁岛非相关 FTD 患者的临床、神经心理学和影像学特征，这些患者携带 TARDBP 突变 p.A382T。此外，我们还回顾了以前文献中描述的具有 TARDBP 突变的非相关 FTD 病例。TARDBP 的 p.A382T 错义突变存在于我们的 FTD 队列中 23 例家族性病例的 21.7%（5/23），而在散发性患者中无一例存在。5 例患者中有 3 例表现为颞叶变异型 FTD，4 例 MRI 显示颞叶优势受累。对具有 TARDBP 突变的 FTD 病例的文献回顾显示，在 16 例病例中，有 5 例（31%）临床表型与颞叶变异型 FTD 或语义性痴呆一致，在 16 例病例中有 7 例（43.7%）神经影像学显示颞叶优势受累。我们的研究进一步支持 TARDBP 突变在纯 FTD 及 FTD/ALS 全谱中的致病作用。在具有独特临床模式的 FTD 突变患者中，颞叶优势受累的存在率较高，这可能有助于与其他形式的痴呆/FTD（散发性和家族性）进行鉴别诊断。
