Boen Hanne M, Vandendriessche Bert, Schippers Jolien, Rabaut Laura, Nijak-Paeske Aleksandra, Ponsaerts Peter, Van Craenenbroeck Emeline M, Loeys Bart, Alaerts Maaike
University of Antwerp and Antwerp University Hospital, GENCOR, Cardiovascular Research, Belgium; University of Antwerp, GENCOR, Center of Medical Genetics, Belgium.
University of Antwerp, GENCOR, Center of Medical Genetics, Belgium.
Stem Cell Res. 2024 Dec;81:103536. doi: 10.1016/j.scr.2024.103536. Epub 2024 Aug 14.
Truncating variants in TTN (TTNtv) are present in 15-25 % of patients with idiopathic dilated cardiomyopathy. Interestingly, the pathogenicity of TTNtv seems to be linked to their location within the gene. More proximal I-band TTNtv (TTNtvI) harbour less pathogenic potential than distant A-band TTNtv (TTNtvA). We created isogenic human induced pluripotent stem cell lines (hiPSC) with TTNtvI and TTNtvA using CRISPR/Cas9, for the investigation of the pathomechanism in hiPSC-derived cardiomyocytes (hiPSC-CMs). Exon 48 (E48), located in the I-band, and exon 357 (E357), located in the A-band were targeted.
TTN基因的截短变异（TTNtv）存在于15%至25%的特发性扩张型心肌病患者中。有趣的是，TTNtv的致病性似乎与其在基因中的位置有关。较靠近I带的TTNtv（TTNtvI）的致病潜力低于较远的A带TTNtv（TTNtvA）。我们使用CRISPR/Cas9技术创建了携带TTNtvI和TTNtvA的同基因人类诱导多能干细胞系（hiPSC），用于研究hiPSC衍生的心肌细胞（hiPSC-CMs）中的发病机制。位于I带的第48外显子（E48）和位于A带的第357外显子（E357）被作为靶点。
