Lattuada Chiara, Santangelo Serena, Peverelli Silvia, McGoldrick Philip, Rogaeva Ekaterina, Zinman Lorne, Haase Georg, Géli Vincent, Silani Vincenzo, Robertson Janice, Ratti Antonia, Bossolasco Patrizia
Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Stem Cell Res. 2023 Feb;66:102998. doi: 10.1016/j.scr.2022.102998. Epub 2022 Dec 9.
The most common genetic cause of Amyotrophic Lateral Sclerosis (ALS) is the expansion of a G4C2 hexanucleotide repeat in the C9orf72 gene. The size of the repeat expansion is highly variable and a cut-off of 30 repeats has been suggested as the lower pathological limit. Repeat size variability has been observed intergenerationally and intraindividually in tissues from different organs and within the same tissue, suggesting instability of the pathological repeat expansion. In order to study this genomic instability, we established iPSCs from five members of the same family of which four carried a C9orf72 repeat expansion and one was wild-type.
肌萎缩侧索硬化症（ALS）最常见的遗传病因是C9orf72基因中G4C2六核苷酸重复序列的扩增。重复序列扩增的大小高度可变，有人提出30次重复为较低的病理下限。在不同器官的组织以及同一组织内，已观察到重复序列大小在代际间和个体内存在变异性，这表明病理重复序列扩增具有不稳定性。为了研究这种基因组不稳定性，我们从同一家族的五名成员中建立了诱导多能干细胞（iPSC），其中四名携带C9orf72重复序列扩增，一名为野生型。
