title: Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
abstract: 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.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Xu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xiong
authors.forename: Lusi
authors.initials: L
authors.lastname: Zhang
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000818:Animals; D044466:Asian People / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013569:Synapses
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C430845:NLGN4X protein, human; D009419:Nerve Tissue Proteins; C098004:neuroligin 3