Karl-Schöller Franziska, Breyer Maximilian, Klopocki Eva, Üçeyler Nurcan
University Hospital Würzburg, Department of Neurology, 97080 Würzburg, Germany.
University of Würzburg, Institute for Human Genetics, 97074 Würzburg, Germany.
Stem Cell Res. 2025 Aug;86:103711. doi: 10.1016/j.scr.2025.103711. Epub 2025 Apr 10.
Fabry disease (FD) is an X-linked genetic disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency and intracellular globotriaosylceramide (Gb3) accumulation. To study FD-associated pathomechanisms, we generated an isogenic control induced pluripotent stem cell (iPSC) line (IsoFD-1) from a patient-derived FD-iPSC line (FD-1) carrying the GLA c.1069C>T mutation. Using CRISPR/Cas9 gene correction, we restored the wild-type sequence, confirmed by Sanger sequencing and absence of Gb3 deposits. IsoFD-1 exhibited typical pluripotency markers, normal karyotype, and trilineage differentiation capacity. This line provides a valuable tool for investigating Gb3-related cellular dysfunction in FD.
法布里病（FD）是一种X连锁遗传病，由GLA基因突变引起，导致α-半乳糖苷酶A缺乏和细胞内球三糖神经酰胺（Gb3）蓄积。为了研究与FD相关的发病机制，我们从携带GLA基因c.1069C>T突变的患者来源的FD诱导多能干细胞（iPSC）系（FD-1）中生成了一个等基因对照iPSC系（IsoFD-1）。通过CRISPR/Cas9基因校正，我们恢复了野生型序列，经桑格测序和无Gb3沉积物证实。IsoFD-1表现出典型的多能性标志物、正常核型和三系分化能力。该细胞系为研究FD中与Gb3相关的细胞功能障碍提供了一个有价值的工具。
