Screening for Neuroligin 4 (NLGN4) truncating and transmembrane domain mutations in schizophrenia

Sand, Philipp; Langguth, Berthold; Hajak, Goeran; Perna, Martin; Přikryl, Radovan; Kučerová, Hana Přikrylová; Češková, Eva; Kick, Christian; Stoertebecker, P.; Eichhammer, Peter

doi:10.1016/j.schres.2005.11.003

Cited by 14 publications

(5 citation statements)

References 8 publications

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“…The neurexin-neuroligin molecules are not implicated in schizophrenia [121]. The Scottish translocation that led to the discovery of DISC1 removes interaction between NDELI/NUDEL with DISC1 [122], [123].…”

Section: Loss Of Function Of Dual Constraint Molecules In the Dlpc Of Subjects With Schizophreniamentioning

confidence: 99%

Dual Constraints on Synapse Formation and Regression in Schizophrenia: Neuregulin, Neuroligin, Dysbindin, DISC1, MuSK and Agrin

2008

Aust N Z J Psychiatry

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During adolescence there is a loss of approximately 30% of the synapses formed in the cortex during childhood. Comprehensive studies of the visual cortex show that this loss of synapses does not occur as a consequence of less appropriate projections being eliminated in favour of more appropriate ones. Rather it seems that synapses with low efficacy for transmission are eliminated in favour of those with higher efficacy. The loss of low-efficacy synapses is known, on theoretical grounds, to enhance the function of neural networks, but large synapse losses lead to failure of network function. In the dorsolateral prefrontal cortex (DLPC) of those suffering from schizophrenia the number of synapses is relatively very low, approximately 60% lower than that observed in normal childhood. It is not known if this is due to an additional loss over that during normal adolescence or whether it results from a failure to form a normal complement of synapses during childhood. The first study of synapse loss in the mammalian nervous system was made on the neuromuscular junction at Sydney University in 1974. Since then this junction has provided principal insights into the molecular basis of synapse formation and regression, so providing a paradigm for investigations of these phenomena in the DLPC. For example the molecules muscle-specific receptor tyrosine kinase (MuSK), agrin and neuregulin have been identified and their critical roles in the formation and maintenance of synapses elucidated. Loss of function of MuSK or agrin leads to failure of neuromuscular synapse formation as well as a loss of approximately 30% of excitatory synapses in the cortex. Similar synapse loss occurs on failure of neuregulin in vitro and of neuroligin in vivo. It is suggested that three important questions need to be answered: first, over what development period are the synapse numbers in DLPC of subjects with schizophrenia lower than normal; second, what are the relative importance of MuSK/agrin, neuregulin/ErB and neurexin/neuroligin in synapse formation and regression in the DLPC; and third, to what extent have these molecules gone awry in schizophrenia.

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Section: Loss Of Function Of Dual Constraint Molecules In the Dlpc Of Subjects With Schizophreniamentioning

confidence: 99%

Dual Constraints on Synapse Formation and Regression in Schizophrenia: Neuregulin, Neuroligin, Dysbindin, DISC1, MuSK and Agrin

2008

Aust N Z J Psychiatry

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“…Studies conducted in 2005 and 2006, failed to identify the variants in the NLGN4Y gene in autistic patients. 15,16 But later several studies, record polymorphisms of NLGN4Y gene involved in neurodevelopmental disorder and synaptic functions have been associated with autism. 17,18 Peripheral blood NLGN4Y gene expression showed an increased risk of autism in children with XYY symptoms.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India

Hegde

Kulkarni³

et al. 2021

Glob Med Genet

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Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population. Aim The present study hypothesizes that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [NLGN4Y] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India. Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid. Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [NLGN4Y] gene especially in the male predominance of autism in Indian autistic population.

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“…The genetics of schizophrenia are complex and analysis of genetic data is difficult. In patients with schizophrenia, researchers have identified mutations in the NL2 [ 137 ] and NL4 [ 186 ] genes.…”

Section: Neuroligins In the ‘Synaptopathy’mentioning

confidence: 99%

Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins

et al. 2022

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Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins.

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Screening for Neuroligin 4 (NLGN4) truncating and transmembrane domain mutations in schizophrenia

Cited by 14 publications

References 8 publications

Dual Constraints on Synapse Formation and Regression in Schizophrenia: Neuregulin, Neuroligin, Dysbindin, DISC1, MuSK and Agrin

Dual Constraints on Synapse Formation and Regression in Schizophrenia: Neuregulin, Neuroligin, Dysbindin, DISC1, MuSK and Agrin

Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India

Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins

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