Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair
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) li...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506125000613 |
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| author | Franziska Karl-Schöller Maximilian Breyer Eva Klopocki Nurcan Üçeyler |
| author_facet | Franziska Karl-Schöller Maximilian Breyer Eva Klopocki Nurcan Üçeyler |
| author_sort | Franziska Karl-Schöller |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-94599dec186a46bcb9dd7f0b4f77cfaf |
| institution | DOAJ |
| issn | 1873-5061 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj-art-94599dec186a46bcb9dd7f0b4f77cfaf2025-08-20T03:10:46ZengElsevierStem Cell Research1873-50612025-08-018610371110.1016/j.scr.2025.103711Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repairFranziska Karl-Schöller0Maximilian Breyer1Eva Klopocki2Nurcan Üçeyler3University Hospital Würzburg, Department of Neurology, 97080 Würzburg, GermanyUniversity Hospital Würzburg, Department of Neurology, 97080 Würzburg, GermanyUniversity of Würzburg, Institute for Human Genetics, 97074 Würzburg, GermanyUniversity Hospital Würzburg, Department of Neurology, 97080 Würzburg, Germany; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1873506125000613 |
| spellingShingle | Franziska Karl-Schöller Maximilian Breyer Eva Klopocki Nurcan Üçeyler Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair Stem Cell Research |
| title | Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair |
| title_full | Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair |
| title_fullStr | Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair |
| title_full_unstemmed | Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair |
| title_short | Generation of a gene-corrected human isogenic iPSC line from a patient with Fabry disease carrying the GLA variant c.1069C>T using CRISPR/Cas9-mediated homology directed repair |
| title_sort | generation of a gene corrected human isogenic ipsc line from a patient with fabry disease carrying the gla variant c 1069c t using crispr cas9 mediated homology directed repair |
| url | http://www.sciencedirect.com/science/article/pii/S1873506125000613 |
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