Neurexins and neuropsychiatric disorders. (February 2018)

• Record Type: Journal Article
• Authors: Kasem, Enas; Kurihara, Taiga; Tabuchi, Katsuhiko
• Is Part Of: Neuroscience research. Volume 127(2018)
• Page Start: 53
• Page End: 60
• Publication Date: 2018-02
• Subjects: ADHD attention deficit hyperactivity disorder -- ASD autism spectrum disorders -- CGH comparative genomic hybridization -- CHO carbohydrate attachment -- CNV copy number variations -- DGAP developmental genome anatomy project -- FISH fluorescent in situ hybridization -- GWAS genome-wide association studies -- ID intellectual disability -- LNS laminin/neurexin/sex hormone–binding globulin -- NRXN human neurexin gene -- Nrxn rodent neurexin gene -- NSID non-syndromic intellectual disability -- PPI prepulse inhibition -- PTHS Pitt-Hopkins syndrome -- QMPSF quantitative multiplex PCR of the short fluorescent fragments -- SNP single nucleotide polymorphisms -- WGSA hole-genome sampling analyses; Synapse -- Neurexins -- Attention deficit hyperactivity disorder -- Autism spectrum disorders -- Intellectual disability -- Pitt-Hopkins syndrome -- Schizophrenia; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2017.10.012
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Neurexins (NRXNs) have been implicated in wide variety of neuropsychiatric disorders. Bi-allelic NRXN1 deficiency causes developmental disorders phenotypically resembling Pitt-Hopkins syndrome. Rodent Nrxn mutant models exhibit behavioral abnormalities reminiscent of neuropsychiatric disorders. Abstract: Neurexins are a family of presynaptic single-pass transmembrane proteins that act as synaptic organizers in mammals. The neurexins consist of three genes (NRXN1, NRXN2, and NRXN3), each of which produces a longer α- and shorter β-form. Genomic alterations in NRXN genes have been identified in a wide variety of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, intellectual disability (ID), and addiction. Remarkably, a bi-allelic deficiency of NRXN1 was recently linked to Pitt-Hopkins syndrome. The fact that some mono-allelic functional variants of NRXNs are also found in healthy controls indicates that other genetic or environmental factors affect the penetrance of NRXN deficiency. In this review, we summarize the common research methods and representative results of human genetic studies that have implicated NRXN variants in various neuropsychiatric disorders. We also summarize studies of rodent models with NRXN deficiencies that complement our knowledge of human genetics.