Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
Dement Geriatr Cogn Disord. 2009;28(5):471-5. doi: 10.1159/000260046. Epub 2009 Nov 23.
BACKGROUND/AIMS: Alterations in gene dosage have recently been associated with neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and deletions of the progranulin (PGRN) locus were recently described in patients with frontotemporal lobar degeneration (FTLD). FTLD is a genetically complex neurodegenerative disorder with mutations in the PGRN and the microtubule-associated protein tau (MAPT) genes being the most common known causes of familial FTLD. In this study, we investigated 39 patients with FTLD, previously found negative for mutations in PGRN and MAPT, for copy number alterations of these 2 genes.
Gene dosage analysis of PGRN and MAPT was performed using multiplex ligation-dependent probe amplification.
We did not identify any PGRN or MAPT gene dosage variations in the 39 FTLD patients investigated.
We therefore conclude that alterations in gene copy number of PGRN and MAPT are not a cause of disease in this collection of FTLD patients.
背景/目的：基因剂量的改变最近与神经退行性疾病相关，如阿尔茨海默病和帕金森病，并且在额颞叶变性（FTLD）患者中最近描述了颗粒体蛋白（PGRN）基因座的缺失。FTLD 是一种遗传复杂的神经退行性疾病，PGRN 和微管相关蛋白 tau（MAPT）基因的突变是最常见的家族性 FTLD 的已知原因。在这项研究中，我们研究了 39 名 FTLD 患者，这些患者先前在 PGRN 和 MAPT 基因中未发现突变，检测了这两个基因的拷贝数改变。
使用多重连接依赖性探针扩增对 PGRN 和 MAPT 的基因剂量进行分析。
我们没有在 39 名 FTLD 患者中发现 PGRN 或 MAPT 基因剂量的任何变化。
因此，我们得出结论，PGRN 和 MAPT 的基因拷贝数改变不是本批 FTLD 患者疾病的原因。
