Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia
Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia
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DOI：
10.1016/j.neurobiolaging.2008.01.005
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发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Bruni, Amalia C.
中科院分区：
文献类型：
--
作者：
Bernardi, Livia;Tomaino, Carmine;Bruni, Amalia C.
背景：额颞叶痴呆是一种临床和遗传异质性综合征。两个基因的突变，微管相关蛋白Tau（MAPT）和前粒蛋白（PGRN），和很少的早老素突变，已经与这种disorder.Objective：为了调查在一组MAPT基因突变阴性的家族性早发性额颞叶痴呆（f-EOFTD）患者中PGRN，PSEN 1，PSEN 2和APP突变的存在。我们前瞻性研究了17例诊断为f-EOFTD的无关受试者（1例神经病理学证实为FTD-Ub+）。在这些受试者中，8个属于8个常染色体显性遗传的家庭彼此无关，和9个至少有一个第一度的相对影响dementions.Results：我们确定了两个新的杂合突变在两个无关的患者，Cys 139 Arg的PGRN基因和Val 412 Ile的PSEN 1基因。结论：早发性f-FTD仍然是一种异质性疾病从遗传的角度来看。在我们的样本中PGRN突变频率较低。PSEN 1新突变的存在提示，当MAPT和PGRN基因筛查阴性时，应进行早老素分子研究。(C)2008年爱思唯尔公司All rights reserved.
Background: Frontotemporal dementia is a clinically and genetically heterogeneous syndrome. Mutations in two genes, Microtubule Associated Protein Tau (MAPT) and Progranulin (PGRN), and rarely Presenilin mutations, have been causally linked to this disorder.Objective: To investigate the presence of PGRN, PSEN1, PSEN2 and APP mutations in a group of familial early-onset frontotemporal dementia (f-EOFTD) patients negative for MAPT gene mutations.Subjects and methods: We prospectively studied 17 unrelated subjects diagnosed with f-EOFTD (one case neuropathologically confirmed as FTD-Ub+). Among these subjects eight belonged to eight autosomal dominant families unrelated to each other, and nine had at least one first degree relative affected by dementia.Results: We identified two novel heterozygous mutations in two unrelated patients, Cys139Arg in the PGRN gene and Val412Ile in the PSEN1 gene.Conclusions: Early-onset f-FTD remains a heterogeneous disorder from a genetic point of view. PGRN mutation frequency was low in our sample. The presence of a novel PSEN1 mutation suggests that presenilin molecular studies should be per-formed when screening for MAPT and PGRN genes is negative. (C) 2008 Elsevier Inc. All rights reserved.