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Copy number variants in neurexin genes: phenotypes and mechanisms
Neurexins are central to trans-synaptic cell adhesion and signaling during synapse specification and maintenance. The past two decades of human genetics research have identified structural variations in the neurexin gene family, in particular NRXN1 copy number variants (CNVs), implicated in multiple...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491281/ https://www.ncbi.nlm.nih.gov/pubmed/33756113 http://dx.doi.org/10.1016/j.gde.2021.02.010 |
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author | Fuccillo, Marc V Pak, ChangHui |
author_facet | Fuccillo, Marc V Pak, ChangHui |
author_sort | Fuccillo, Marc V |
collection | PubMed |
description | Neurexins are central to trans-synaptic cell adhesion and signaling during synapse specification and maintenance. The past two decades of human genetics research have identified structural variations in the neurexin gene family, in particular NRXN1 copy number variants (CNVs), implicated in multiple neuropsychiatric and developmental disorders. The heterogeneity and reduced penetrance of NRXN1 deletions, in addition to the pleiotropic, circuit-specific functions of NRXN1, present substantial obstacles to understanding how compromised NRXN1 function predisposes individuals to neuropsychiatric disorders. Here, we provide an updated review of NRXN1 genetics in disease, followed by recently published work using both human induced pluripotent stem cell (iPSC) derived systems and animal models to understand the mechanisms of disease pathophysiology. Finally, we suggest our outlook on how the field should progress to improve our understanding of neurexin mediated disease pathogenesis. We believe that understanding how structural genetic variants in NRXN1 contribute to disease pathophysiology requires parallel approaches in iPSC and mouse model systems, each leveraging their unique strengths — analysis of genetic interactions and background effects in iPSCs and neural circuit and behavioral analysis in mice. |
format | Online Article Text |
id | pubmed-8491281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-84912812021-10-05 Copy number variants in neurexin genes: phenotypes and mechanisms Fuccillo, Marc V Pak, ChangHui Curr Opin Genet Dev Article Neurexins are central to trans-synaptic cell adhesion and signaling during synapse specification and maintenance. The past two decades of human genetics research have identified structural variations in the neurexin gene family, in particular NRXN1 copy number variants (CNVs), implicated in multiple neuropsychiatric and developmental disorders. The heterogeneity and reduced penetrance of NRXN1 deletions, in addition to the pleiotropic, circuit-specific functions of NRXN1, present substantial obstacles to understanding how compromised NRXN1 function predisposes individuals to neuropsychiatric disorders. Here, we provide an updated review of NRXN1 genetics in disease, followed by recently published work using both human induced pluripotent stem cell (iPSC) derived systems and animal models to understand the mechanisms of disease pathophysiology. Finally, we suggest our outlook on how the field should progress to improve our understanding of neurexin mediated disease pathogenesis. We believe that understanding how structural genetic variants in NRXN1 contribute to disease pathophysiology requires parallel approaches in iPSC and mouse model systems, each leveraging their unique strengths — analysis of genetic interactions and background effects in iPSCs and neural circuit and behavioral analysis in mice. 2021-06 2021-03-21 /pmc/articles/PMC8491281/ /pubmed/33756113 http://dx.doi.org/10.1016/j.gde.2021.02.010 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Fuccillo, Marc V Pak, ChangHui Copy number variants in neurexin genes: phenotypes and mechanisms |
title | Copy number variants in neurexin genes: phenotypes and mechanisms |
title_full | Copy number variants in neurexin genes: phenotypes and mechanisms |
title_fullStr | Copy number variants in neurexin genes: phenotypes and mechanisms |
title_full_unstemmed | Copy number variants in neurexin genes: phenotypes and mechanisms |
title_short | Copy number variants in neurexin genes: phenotypes and mechanisms |
title_sort | copy number variants in neurexin genes: phenotypes and mechanisms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491281/ https://www.ncbi.nlm.nih.gov/pubmed/33756113 http://dx.doi.org/10.1016/j.gde.2021.02.010 |
work_keys_str_mv | AT fuccillomarcv copynumbervariantsinneurexingenesphenotypesandmechanisms AT pakchanghui copynumbervariantsinneurexingenesphenotypesandmechanisms |