title: Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.
abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, absence or delay in language development, and stereotyped or repetitive behaviors. Genetic studies show that neurexin-neuroligin (NRXN-NLGN) pathway genes contribute susceptibility to ASD, which include cell adhesion molecules NLGN3, NLGN4 and scaffolding proteins SHANK2 and SHANK3. Neuroligin proteins play an important role in synaptic function and trans-synaptic signaling by interacting with presynaptic neurexins. Shank proteins are scaffolding molecules of excitatory synapses, which function as central organizers of the postsynaptic density. Sequence level mutations and structural variations in these genes have been identified in ASD cases, while few studies were performed in Chinese population. In this study, we examined the copy numbers of four genes NLGN4, NLGN3, SHANK2, and SHANK3 in 285 ASD cases using multiplex fluorescence competitive polymerase chain reaction (PCR). We also screened the regulatory region including the promoter region and 5'/3' untranslated regions (UTR) and the entire coding region of NLGN4 in a cohort of 285 ASD patients and 384 controls by direct sequencing of genomic DNA using the Sanger method. DNA copy number calculation in four genes showed no deletion or duplication in our cases. No missense mutations in NLGN4 were identified in our cohort. Association analysis of 6 common SNPs in NLGN4 did not find significant difference between ASD cases and controls. These findings showed that these genes may not be major disease genes in Chinese ASD cases.
authors.affiliation: The MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yasong
authors.initials: Y
authors.lastname: Du
authors.forename: Wenwen
authors.initials: W
authors.lastname: Liu
authors.forename: Caohua
authors.initials: C
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Gong
mesh_terms: D020413:3' Untranslated Regions; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D002681:China; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C430845:NLGN4X protein, human; D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human; C492357:SHANK3 protein, human; C098004:neuroligin 3