Tedde Andrea, Bartoli Antonella, Piaceri Irene, Ferrara Sara, Bagnoli Silvia, Serio Antonio, Sorbi Sandro, Nacmias Benedetta
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy.
Villa Serena Hospital, Città S. Angelo, Pescara, Italy.
Neurosci Lett. 2016 Jan 1;610:150-3. doi: 10.1016/j.neulet.2015.11.004. Epub 2015 Nov 5.
Alzheimer's disease (AD) is a neurodegenerative disease affecting over 20 million people worldwide, mainly adult subjects in advanced age. Over 240 different fully penetrant autosomal dominant mutations in 532 families around the world have been described in three genes [i.e., amyloid precursor protein (APP), and presenilins (PSEN1 and PSEN2)] causing 50% of all Familial AD. We report a new mutation (p.Ile408Thr, c. 1223T>C) in the PSEN1 gene in one autosomal dominant Late Onset AD patient. The genetic variation occurred in a conserved domain of the protein and was present in the proband and in the younger sister who is likely to be prodromal AD. Thus, we suggest that this variant will have probably a pathogenic effect, hypothesizing a possible key role of this new mutation in the pathogenesis of Alzheimer's disease for this family.
阿尔茨海默病（AD）是一种神经退行性疾病，全球有超过2000万人受其影响，主要是老年成人患者。全世界532个家族中已描述了240多种不同的完全显性常染色体显性突变，这些突变存在于三个基因中[即淀粉样前体蛋白（APP）和早老素（PSEN1和PSEN2）]，导致了50%的家族性AD。我们报告了一名常染色体显性晚发性AD患者的PSEN1基因中的一个新突变（p.Ile408Thr，c. 1223T>C）。该基因变异发生在蛋白质的一个保守结构域中，先证者及其可能处于AD前驱期的妹妹均存在该变异。因此，我们认为该变异可能具有致病作用，并推测这一新突变在该家族阿尔茨海默病的发病机制中可能起关键作用。
