Nrxn1, or Neurexin 1, is a gene encoding presynaptic cell adhesion molecules that are critically involved in synaptogenesis and vesicular neurotransmitter release [3]. Neurexins play important roles in the formation, establishment, and maintenance of synaptic structure and function, with Nrxn1 being a key player in neural connectivity and synaptic function [2,3,5].

Heterozygous deletions of Nrxn1 are associated with a diverse spectrum of phenotypes, including autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, mood disorders, and congenital malformations [1]. The penetrance of these deletions is reduced, and their expressivity is variable, making genetic counseling challenging [1]. The presence of Nrxn1 mutations emphasizes the gene's role in synaptic function in the context of autism spectrum disorder [2]. De novo mutations and copy number deletions in Nrxn1 also pose a significant risk for schizophrenia, with such deletions leading to long-lasting changes in neuronal networks and implicating synaptic dysfunction [4].

In conclusion, Nrxn1 is essential for synaptic function and neural connectivity. Studies of Nrxn1, particularly through observing the effects of its deletions, have provided insights into its role in various neurodevelopmental, psychiatric, and neurological disorders such as autism spectrum disorder and schizophrenia [1,2,3,4]. These findings help in understanding the neurobiological mechanisms underlying these diseases, potentially paving the way for new therapeutic strategies.

References:

1. Al Shehhi, Maryam, Forman, Eva B, Fitzgerald, Jacqueline E, Gallagher, Louise, Lynch, Sally A. 2018. NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families. In European journal of medical genetics, 62, 204-209. doi:10.1016/j.ejmg.2018.07.015. https://pubmed.ncbi.nlm.nih.gov/30031152/

2. Cooper, Jaimee N, Mittal, Jeenu, Sangadi, Akhila, Mittal, Rahul, Eshraghi, Adrien A. 2024. Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review. In Journal of clinical medicine, 13, . doi:10.3390/jcm13072067. https://pubmed.ncbi.nlm.nih.gov/38610832/

3. Castronovo, Paola, Baccarin, Marco, Ricciardello, Arianna, Sacco, Roberto, Persico, Antonio M. 2019. Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: A systematic review. In Clinical genetics, 97, 125-137. doi:10.1111/cge.13537. https://pubmed.ncbi.nlm.nih.gov/30873608/

4. Sebastian, Rebecca, Jin, Kang, Pavon, Narciso, Aronow, Bruce, Pak, ChangHui. 2023. Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids. In Nature communications, 14, 3770. doi:10.1038/s41467-023-39420-6. https://pubmed.ncbi.nlm.nih.gov/37355690/

5. Hu, Zhonghua, Xiao, Xiao, Zhang, Zhuohua, Li, Ming. 2019. Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders. In Molecular psychiatry, 24, 1400-1414. doi:10.1038/s41380-019-0438-9. https://pubmed.ncbi.nlm.nih.gov/31138894/