Autism is a neurodevelopmental disorder clinically characterized by impairment of social interaction, deficits in verbal communication, as well as stereotypic and repetitive behaviors. Several studies have implicated that abnormal synaptogenesis was involved in the incidence of autism. Neuroligins are postsynaptic cell adhesion molecules and interacted with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, mutation analysis, cellular and mice models hinted neuroligin mutations probably affected synapse maturation and function. In this study, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. These four missense variations were absent in the 453 controls and have not been reported in 1000 Genomes Project. Bioinformatic analysis of the four missense variations revealed that p.G84R and p.A283T were “Probably Damaging”. The variations may cause abnormal synaptic homeostasis and therefore trigger the patients more predisposed to autism. By case–control analysis, we identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95 % CI 2.073–10.592)]. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population.
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We thank the patients and their families for agreeing to participate in this study and special teachers whose participation made this project possible. We also thank Cong Wang and Haoying Hao for sequencing, Jiada Li for manuscript revision. We were appreciated for the help and advices of our colleagues. This study was supported by the National Basic Research Program 973 of China (Grant No. 2012CB 517902, 2010 CB 529601) and the National Natural Science Foundation of China (Grant No. 81330027, 81161120544, 31301023).
Conflict of interest
The authors state no competing interests.
Xiaojuan Xu, Zhimin Xiong and Lusi Zhang contributed equally to this study.
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Xu, X., Xiong, Z., Zhang, L. et al. Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients. Mol Biol Rep 41, 4133–4140 (2014). https://doi.org/10.1007/s11033-014-3284-5