Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency
A rare neurodevelopmental disorder has been linked to a well-conserved splice site variant in the TRAPPC4 gene (c.454 + 3A > G), which causes mis-splicing of TRAPPC4 transcripts and reduced levels of TRAPPC4 protein. Patients present with severe progressive neurological symptoms including seizure...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506124003386 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841543970360918016 |
|---|---|
| author | Riley Hall Tim Sikora Annabelle Suter Jia Yi Kuah John Christodoulou Nicole J Van Bergen |
| author_facet | Riley Hall Tim Sikora Annabelle Suter Jia Yi Kuah John Christodoulou Nicole J Van Bergen |
| author_sort | Riley Hall |
| collection | DOAJ |
| description | A rare neurodevelopmental disorder has been linked to a well-conserved splice site variant in the TRAPPC4 gene (c.454 + 3A > G), which causes mis-splicing of TRAPPC4 transcripts and reduced levels of TRAPPC4 protein. Patients present with severe progressive neurological symptoms including seizures, microcephaly, intellectual disability and facial dysmorphism. We have generated stem cells from fibroblasts of two individuals with the same homozygous TRAPPC4 c.454 + 3A > G pathogenic variant and used CRISPR/Cas9 editing to generate heterozygous gene-corrected isogenic controls. Clones were tested for pluripotency, differentiation potential, genotyped and karyotyped. These iPSC-based models will be used to understand disease mechanisms of TRAPPC4 disorder. |
| format | Article |
| id | doaj-art-3c9c633cc7c64b91b5d7e95d14a72b6f |
| institution | Kabale University |
| issn | 1873-5061 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj-art-3c9c633cc7c64b91b5d7e95d14a72b6f2025-01-13T04:18:42ZengElsevierStem Cell Research1873-50612025-02-0182103640Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiencyRiley Hall0Tim Sikora1Annabelle Suter2Jia Yi Kuah3John Christodoulou4Nicole J Van Bergen5Murdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaMurdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Corresponding author at: Murdoch Children’s Research Institute, Parkville, Victoria, Australia.A rare neurodevelopmental disorder has been linked to a well-conserved splice site variant in the TRAPPC4 gene (c.454 + 3A > G), which causes mis-splicing of TRAPPC4 transcripts and reduced levels of TRAPPC4 protein. Patients present with severe progressive neurological symptoms including seizures, microcephaly, intellectual disability and facial dysmorphism. We have generated stem cells from fibroblasts of two individuals with the same homozygous TRAPPC4 c.454 + 3A > G pathogenic variant and used CRISPR/Cas9 editing to generate heterozygous gene-corrected isogenic controls. Clones were tested for pluripotency, differentiation potential, genotyped and karyotyped. These iPSC-based models will be used to understand disease mechanisms of TRAPPC4 disorder.http://www.sciencedirect.com/science/article/pii/S1873506124003386TRAPPC4TRAPPopathyNeurodevelopmental disorderSeizuresMicrocephalyStem cell |
| spellingShingle | Riley Hall Tim Sikora Annabelle Suter Jia Yi Kuah John Christodoulou Nicole J Van Bergen Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency Stem Cell Research TRAPPC4 TRAPPopathy Neurodevelopmental disorder Seizures Microcephaly Stem cell |
| title | Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency |
| title_full | Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency |
| title_fullStr | Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency |
| title_full_unstemmed | Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency |
| title_short | Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency |
| title_sort | generation and heterozygous repair of human ipsc lines from two individuals with the neurodevelopmental disorder trappc4 deficiency |
| topic | TRAPPC4 TRAPPopathy Neurodevelopmental disorder Seizures Microcephaly Stem cell |
| url | http://www.sciencedirect.com/science/article/pii/S1873506124003386 |
| work_keys_str_mv | AT rileyhall generationandheterozygousrepairofhumanipsclinesfromtwoindividualswiththeneurodevelopmentaldisordertrappc4deficiency AT timsikora generationandheterozygousrepairofhumanipsclinesfromtwoindividualswiththeneurodevelopmentaldisordertrappc4deficiency AT annabellesuter generationandheterozygousrepairofhumanipsclinesfromtwoindividualswiththeneurodevelopmentaldisordertrappc4deficiency AT jiayikuah generationandheterozygousrepairofhumanipsclinesfromtwoindividualswiththeneurodevelopmentaldisordertrappc4deficiency AT johnchristodoulou generationandheterozygousrepairofhumanipsclinesfromtwoindividualswiththeneurodevelopmentaldisordertrappc4deficiency AT nicolejvanbergen generationandheterozygousrepairofhumanipsclinesfromtwoindividualswiththeneurodevelopmentaldisordertrappc4deficiency |