These are the first experimental data that associate a deletion of Neurexin 1α with alterations in behaviours relevant to autism spectrum disorder across development and highlight the importance of assessing the developmental trajectory in mouse models of neurodevelopmental disorders.This article is protected by copyright.All rights reserved.
The spectrum of phenotypes associated with heterozygous deletions of neurexin-1 (NRXN1) is diverse and includes: autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, mood disorders and congenital malformations.
We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion.
The two deletions upstream of the NRXN1 gene were found to segregate with psychiatric disorders in the family and further similar deletions have been observed in patients diagnosed with autism spectrum disorder.
Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%).
Our data support previous observations that NRXN1 may be pathogenic in a wide variety of psychiatric diseases, including autism spectrum disorder, global developmental delay, anxiety, and depression.