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
We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta ( ) 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 paren...
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Published in | Frontiers in neuroscience Vol. 17; p. 1302470 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
08.01.2024
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta (
) 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
genetic variation was corrected in iPSC lines from two probands by CRISPR/Cas9 gene editing. Cortical neurons were produced by directed,
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Idris Long, University of Science Malaysia (USM), Malaysia Reviewed by: Derek J. C. Tai, Massachusetts General Hospital and Harvard Medical School, United States; Jiaxu Wang, Genome Institute of Singapore, Singapore |
ISSN: | 1662-4548 1662-453X 1662-453X |
DOI: | 10.3389/fnins.2023.1302470 |