Neurology II, Department of Neuroscience, University of Turin, Turin, Italy.
Dement Geriatr Cogn Disord. 2009;28(3):239-43. doi: 10.1159/000241876. Epub 2009 Sep 25.
BACKGROUND/AIM: Recent studies showed that TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, is a major pathological protein in both sporadic and familial frontotemporal lobar degeneration (FTLD). The aim of this study was to search for mutations of the TARDBP gene in the disease.
We sequenced the TARDBP gene in 172 unrelated FTLD patients recruited from 2 Italian memory clinics.
We identified 3 different variants of the TARDBP gene in 12 FTLD patients. Three patients showed a silent variant, Ala66Ala (c.332T --> C) in exon 2. A novel heterozygous mutation was found in intron 4 (c.543 + 51A --> G) in 1 patient, which is not located at the splicing site. Finally, a c.208C --> T variant in the 3' untranslated region was detected in 8 probands. None of the aforementioned variants were predicted to affect TDP-43. Hence, pathogenic mutations were not identified in any of the FTLD cases.
Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD.
背景/目的：最近的研究表明，TAR DNA 结合蛋白 43（TDP-43），由 TARDBP 基因编码，是散发性和家族性额颞叶变性（FTLD）的主要病理蛋白。本研究旨在寻找 TARDBP 基因在该疾病中的突变。
我们对 2 家意大利记忆诊所招募的 172 名无关 FTLD 患者进行了 TARDBP 基因测序。
我们在 12 名 FTLD 患者中发现了 TARDBP 基因的 3 种不同变体。3 名患者在第 2 外显子中表现为沉默变体 Ala66Ala（c.332T --> C）。1 名患者在第 4 内含子中发现了一个新的杂合突变（c.543 + 51A --> G），该突变不在剪接位点。最后，在 8 名先证者中检测到 3'非翻译区的 c.208C --> T 变体。上述变体均未预测会影响 TDP-43。因此，在任何 FTLD 病例中均未发现致病性突变。
我们的研究与不同人群的先前研究一致，没有证据表明 TARDBP 基因在 FTLD 中存在主要遗传作用。
