Mutation Screening of the Neurexin 1 Gene in Thai Patients with Intellectual Disability and Autism Spectrum Disorder

Yangngam, Supaporn; Plong-On, Oradawan; Sripo, Thanya; Roongpraiwan, Rawiwan; Hansakunachai, Tippawan; Wirojanan, Juthamas; Sombuntham, Tasnawat; Ruangdaraganon, Nichara; Limprasert, Pornprot

doi:10.1089/gtmb.2014.0003

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…The top 10 most strongly autism-correlating empirically-identified transcripts/proteins are depicted in a heatmap format in Figures 6D,E (elevated compared to control = red; decreased compared to control = green). From the transcript analysis, we identified the involvement of neurexin 1 (Yangngam et al, 2014 ) and Wolframin syndrome 1 (Wfs1; Chakrabarti et al, 2009 ). From the protein analysis, we again identified Wfs1 as a strong autism-related link, Fam120c (De Wolf et al, 2014 ), and Bassoon (Bsn; Yoshida et al, 2011 ).…”

Section: Resultsmentioning

confidence: 99%

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder

et al. 2015

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Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including “axon guidance” and “regulation of actin cytoskeleton.” In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.

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Section: Resultsmentioning

confidence: 99%

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder

et al. 2015

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“…Loss-of-function variants in NRXN1 have been identified in patients with ASD in multiple cohort studies (Marshall et al, 2008; Morrow et al, 2008; Glessner et al, 2009). A wide spectrum of developmental disorders including ID without ASD (Camacho-Garcia et al, 2012; Yangngam et al, 2014), language delay, mild dysmorphic features, and hypotonia (Ching et al, 2010), as well as neuropsychiatric conditions like SCZ have also been reported in patients with NRXN1 variants. In contrast, variants in NRXN2 and NRXN3 are much rarer, but accumulating reports provide evidence supporting an association between these two genes and ASD, as well as other neurodevelopmental and neuropsychiatric conditions (Gauthier et al, 2011; Vaags et al, 2012; Yuan et al, 2018).…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

Synaptopathology Involved in Autism Spectrum Disorder

Guang

Pang

Deng

et al. 2018

Front. Cell. Neurosci.

217

172

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Autism spectrum disorder (ASD) encompasses a group of multifactorial neurodevelopmental disorders characterized by impaired social communication, social interaction and repetitive behaviors. ASD affects 1 in 59 children, and is about 4 times more common among boys than among girls. Strong genetic components, together with environmental factors in the early stage of development, contribute to the pathogenesis of ASD. Multiple studies have revealed that mutations in genes like NRXN, NLGN, SHANK, TSC1/2, FMR1, and MECP2 converge on common cellular pathways that intersect at synapses. These genes encode cell adhesion molecules, scaffolding proteins and proteins involved in synaptic transcription, protein synthesis and degradation, affecting various aspects of synapses including synapse formation and elimination, synaptic transmission and plasticity. This suggests that the pathogenesis of ASD may, at least in part, be attributed to synaptic dysfunction. In this article, we will review major genes and signaling pathways implicated in synaptic abnormalities underlying ASD, and discuss molecular, cellular and functional studies of ASD experimental models.

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“…Neurexins ( NRXN ) are synaptic adhesion proteins that localize to the membrane of the presynapse and bind Neuroligins (NLGNs), which are localized on the postsynaptic membrane. There are three genes within the NRXN family ( NRXN1 , NRXN2 , and NRXN3 ) with multiple mutations or copy number variations having been identified in NRXN family members in ASD diagnoses (Feng et al, 2006 ; Autism Genome Project Consortium et al, 2007 ; Bremer et al, 2011 ; Yangngam et al, 2014 ). NRXN1 mutations have also been identified in multiple neuropsychiatric disorders, including Tourette syndrome, schizophrenia, ADHD and bipolar disorder (Stone et al, 2008 ; Guilmatre et al, 2009 ; Zhang et al, 2009 ; Sundaram et al, 2010 ; Lionel et al, 2011 ).…”

Section: Alterations In Synaptic Components In Asdmentioning

confidence: 99%

Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity

Gilbert

Man

2017

Front. Cell. Neurosci.

211

151

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Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence. Highlights• Autism spectrum disorder (ASD) has a prevalence of 1 in 68 children in the United States.• ASDs are highly heterogeneous in their genetic basis.• ASDs share common features at the cellular and molecular levels in the brain.• Most ASD genes are implicated in neurogenesis, structural maturation, synaptogenesis and function.

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Mutation Screening of the Neurexin 1 Gene in Thai Patients with Intellectual Disability and Autism Spectrum Disorder

Abstract: Mutation screening of the NRXN1gene in patients with ID and ASD may be useful to identify potential variants predisposing to ID and ASD. However, further studies utilizing protein functional analysis of the novel variants are required for a more definite conclusion.

Cited by 14 publications

References 21 publications

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder

Synaptopathology Involved in Autism Spectrum Disorder

Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity

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