Behnam Mahdiyeh, Ghorbani Fatemeh, Shin Jin-Hong, Kim Dae-Seong, Jang Hojung, Nouri Narges, Sedghi Maryam, Salehi Mansoor, Ansari Behnaz, Basiri Keivan
Medical Genetics Laboratory of Genome, Isfahan, Iran.
Isfahan University, Isfahan, Iran.
Gene. 2015 Oct 1;570(1):150-2. doi: 10.1016/j.gene.2015.06.033. Epub 2015 Jun 15.
Frontotemporal dementia is a neurodegenerative disorder among adults. An autosomal-dominantly form of frontotemporal dementia and parkinsonism linked to chromosome 17q21.2 (FTDP-17) was defined in 1996. The MAPT gene is responsible for the major cases of FTDP-17, and tau also has a role in Alzheimer's disease. So far, different FTDP-17 causing mutations have been identified in the MAPT gene. Among different MAPT mutations, the R406W mutation has been reported with a phenotype resembling Alzheimer's disease. Nonetheless, in this study we have identified the first homozygous case of R406W mutation in an Iranian family which shows characteristics of FTDP, just like the other heterozygous mutations of MAPT. This study clearly indicates that homozygous R406W mutation could result in FTDP phenotype. Our family confirms heterogeneity in the clinical phenotype of MAPT mutations; moreover, in the R406W mutation, a dosage effect is likely to contribute to this clinical heterogeneity.
额颞叶痴呆是成年人中的一种神经退行性疾病。1996年定义了一种与17号染色体q21.2相关的常染色体显性遗传形式的额颞叶痴呆和帕金森综合征（FTDP-17）。微管相关蛋白tau（MAPT）基因是FTDP-17主要病例的病因，并且tau蛋白在阿尔茨海默病中也起作用。到目前为止，已在MAPT基因中鉴定出不同的导致FTDP-17的突变。在不同的MAPT突变中，R406W突变被报道具有类似于阿尔茨海默病的表型。尽管如此，在本研究中，我们在一个伊朗家庭中鉴定出了首例R406W突变的纯合子病例，该病例表现出FTDP的特征，就像MAPT的其他杂合突变一样。这项研究清楚地表明，纯合子R406W突变可导致FTDP表型。我们的家系证实了MAPT突变临床表型的异质性；此外，在R406W突变中，剂量效应可能导致这种临床异质性。
