Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fuccillo, Marc V, Pak, ChangHui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
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
_version_ 1784578708447690752
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