Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines
<p dir="ltr">We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta (NAPB) gene inherited by monozygotic triplets contributed to their phenotype of early-onset epilepsy and autism. Induced pluripotent stem cell (iPSC) lines were generated from a...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2024
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1864513510201884672 |
|---|---|
| author | Gowher Ali (14152593) |
| author2 | Kyung Chul Shin (13913556) Wesal Habbab (17346961) Ghaneya Alkhadairi (17346964) Alice AbdelAleem (17753799) Fouad A. AlShaban (17753802) Yongsoo Park (761850) Lawrence W. Stanton (6707191) |
| author2_role | author author author author author author author |
| author_facet | Gowher Ali (14152593) Kyung Chul Shin (13913556) Wesal Habbab (17346961) Ghaneya Alkhadairi (17346964) Alice AbdelAleem (17753799) Fouad A. AlShaban (17753802) Yongsoo Park (761850) Lawrence W. Stanton (6707191) |
| author_role | author |
| dc.creator.none.fl_str_mv | Gowher Ali (14152593) Kyung Chul Shin (13913556) Wesal Habbab (17346961) Ghaneya Alkhadairi (17346964) Alice AbdelAleem (17753799) Fouad A. AlShaban (17753802) Yongsoo Park (761850) Lawrence W. Stanton (6707191) |
| dc.date.none.fl_str_mv | 2024-01-08T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fnins.2023.1302470 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Characterization_of_a_loss-of-function_NSF_attachment_protein_beta_mutation_in_monozygotic_triplets_affected_with_epilepsy_and_autism_using_cortical_neurons_from_proband-derived_and_CRISPR-corrected_induced_pluripotent_stem_cell_lines/26389039 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences cortical neuron NAPB iPSC CRISPR/Cas9 exon skipping |
| dc.title.none.fl_str_mv | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta (NAPB) gene inherited by monozygotic triplets contributed to their phenotype of early-onset epilepsy and autism. Induced pluripotent stem cell (iPSC) lines were generated from all three probands and both parents. The NAPB genetic variation was corrected in iPSC lines from two probands by CRISPR/Cas9 gene editing. Cortical neurons were produced by directed, in vitro differentiation from all iPSC lines. These cell line-derived neurons enabled us to determine that the genetic variation in the probands causes exon skipping and complete absence of NAPB protein. Electrophysiological and transcriptomic comparisons of cortical neurons derived from parents and probands cell lines indicate that loss of NAPB function contributes to alterations in neuronal functions and likely contributed to the impaired neurodevelopment of the triplets.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Neuroscience<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fnins.2023.1302470" target="_blank">https://dx.doi.org/10.3389/fnins.2023.1302470</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_e913fabede4eb2cb80223194c1814886 |
| identifier_str_mv | 10.3389/fnins.2023.1302470 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26389039 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell linesGowher Ali (14152593)Kyung Chul Shin (13913556)Wesal Habbab (17346961)Ghaneya Alkhadairi (17346964)Alice AbdelAleem (17753799)Fouad A. AlShaban (17753802)Yongsoo Park (761850)Lawrence W. Stanton (6707191)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesNeurosciencescortical neuronNAPBiPSCCRISPR/Cas9exon skipping<p dir="ltr">We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta (NAPB) gene inherited by monozygotic triplets contributed to their phenotype of early-onset epilepsy and autism. Induced pluripotent stem cell (iPSC) lines were generated from all three probands and both parents. The NAPB genetic variation was corrected in iPSC lines from two probands by CRISPR/Cas9 gene editing. Cortical neurons were produced by directed, in vitro differentiation from all iPSC lines. These cell line-derived neurons enabled us to determine that the genetic variation in the probands causes exon skipping and complete absence of NAPB protein. Electrophysiological and transcriptomic comparisons of cortical neurons derived from parents and probands cell lines indicate that loss of NAPB function contributes to alterations in neuronal functions and likely contributed to the impaired neurodevelopment of the triplets.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Neuroscience<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fnins.2023.1302470" target="_blank">https://dx.doi.org/10.3389/fnins.2023.1302470</a></p>2024-01-08T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fnins.2023.1302470https://figshare.com/articles/journal_contribution/Characterization_of_a_loss-of-function_NSF_attachment_protein_beta_mutation_in_monozygotic_triplets_affected_with_epilepsy_and_autism_using_cortical_neurons_from_proband-derived_and_CRISPR-corrected_induced_pluripotent_stem_cell_lines/26389039CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/263890392024-01-08T03:00:00Z |
| spellingShingle | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines Gowher Ali (14152593) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences cortical neuron NAPB iPSC CRISPR/Cas9 exon skipping |
| status_str | publishedVersion |
| title | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| title_full | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| title_fullStr | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| title_full_unstemmed | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| title_short | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| title_sort | Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences cortical neuron NAPB iPSC CRISPR/Cas9 exon skipping |