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Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders.
Brain Res Bull. 2017 03; 129:82-90.BR

Abstract

Synaptic cell adhesion molecules (SCAMs) are a functional category of cell adhesion molecules that connect pre- and postsynapses by the protein-protein interaction via their extracellular cell adhesion domains. Countless numbers of common genetic variants and rare mutations in SCAMs have been identified in the patients with autism spectrum disorders (ASDs). Among these, NRXN and NLGN family proteins cooperatively function at synaptic terminals both of which genes are strongly implicated as risk genes for ASDs. Knock-in mice carrying a single rare point mutation of NLGN3 (NLGN3 R451C) discovered in the patients with ASDs display a deficit in social interaction and an enhancement of spatial learning and memory ability reminiscent of the clinical phenotype of ASDs. NLGN4 knockout (KO) and NRXN2α KO mice also show a deficit in sociability as well as some specific neuropsychiatric behaviors. In this review, we selected NRXNs/NLGNs, CNTNAP2/CNTNAP4, CNTN4, ITGB3, and KIRREL3 as strong ASD risk genes based on SFARI score and summarize the protein structures, functions at synapses, representative discoveries in human genetic studies, and phenotypes of the mutant model mice in light of the pathophysiology of ASDs.

Authors+Show Affiliations

Department of Biological Sciences, Forman Christian College, Zahoor Elahi Rd, Lahore, 54600, Pakistan.Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan; Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, 390-8621, Japan; PRESTO, JST, Saitama, 332-0012, Japan. Electronic address: ktabuchi@shinshu-u.ac.jp.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27743928

Citation

Baig, Deeba Noreen, et al. "Distortion of the Normal Function of Synaptic Cell Adhesion Molecules By Genetic Variants as a Risk for Autism Spectrum Disorders." Brain Research Bulletin, vol. 129, 2017, pp. 82-90.
Baig DN, Yanagawa T, Tabuchi K. Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders. Brain Res Bull. 2017;129:82-90.
Baig, D. N., Yanagawa, T., & Tabuchi, K. (2017). Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders. Brain Research Bulletin, 129, 82-90. https://doi.org/10.1016/j.brainresbull.2016.10.006
Baig DN, Yanagawa T, Tabuchi K. Distortion of the Normal Function of Synaptic Cell Adhesion Molecules By Genetic Variants as a Risk for Autism Spectrum Disorders. Brain Res Bull. 2017;129:82-90. PubMed PMID: 27743928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders. AU - Baig,Deeba Noreen, AU - Yanagawa,Toru, AU - Tabuchi,Katsuhiko, Y1 - 2016/10/12/ PY - 2016/06/13/received PY - 2016/10/08/revised PY - 2016/10/10/accepted PY - 2016/10/25/pubmed PY - 2017/11/8/medline PY - 2016/10/17/entrez KW - Autism spectrum disorders KW - Mouse models KW - Neurexin KW - Neuroligin KW - Synaptic cell adhesion molecules SP - 82 EP - 90 JF - Brain research bulletin JO - Brain Res. Bull. VL - 129 N2 - Synaptic cell adhesion molecules (SCAMs) are a functional category of cell adhesion molecules that connect pre- and postsynapses by the protein-protein interaction via their extracellular cell adhesion domains. Countless numbers of common genetic variants and rare mutations in SCAMs have been identified in the patients with autism spectrum disorders (ASDs). Among these, NRXN and NLGN family proteins cooperatively function at synaptic terminals both of which genes are strongly implicated as risk genes for ASDs. Knock-in mice carrying a single rare point mutation of NLGN3 (NLGN3 R451C) discovered in the patients with ASDs display a deficit in social interaction and an enhancement of spatial learning and memory ability reminiscent of the clinical phenotype of ASDs. NLGN4 knockout (KO) and NRXN2α KO mice also show a deficit in sociability as well as some specific neuropsychiatric behaviors. In this review, we selected NRXNs/NLGNs, CNTNAP2/CNTNAP4, CNTN4, ITGB3, and KIRREL3 as strong ASD risk genes based on SFARI score and summarize the protein structures, functions at synapses, representative discoveries in human genetic studies, and phenotypes of the mutant model mice in light of the pathophysiology of ASDs. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/27743928/Distortion_of_the_normal_function_of_synaptic_cell_adhesion_molecules_by_genetic_variants_as_a_risk_for_autism_spectrum_disorders_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(16)30344-6 DB - PRIME DP - Unbound Medicine ER -