title: Mutation analysis of the NRXN1 gene in a Chinese autism cohort.
abstract: Autism is a brain developmental disorder characterized by impaired social interaction and communication, as well as restricted and repetitive behaviors. The neurexin-1(NRXN1) gene mapped on chromosome 2p16.3 encodes neurexin, a cell adhesion molecule and receptor in the vertebrate nervous system. Rare de novo alterations and copy number variations (CNVs) suggested neurexin-1 as a candidate gene for the pathogenesis of autism, but data on the gene mutation of neurexin-1 in Chinese Han population with autism are limited. By direct sequencing, we analyzed the entire coding regions and associated splice junctions of neurexin-1 in 313 Chinese autism patients. For exons in which non-synonymous variants were identified, sequencing was performed in 500 healthy controls. We identified 22 variants in the neurexin-1 coding regions, including 7 missense variants, 3 deletions, and 12 synonymous mutations. Among them, 3 missense and 3 synonymous variants were not reported in the dbSNP database and absent in 500 control subjects; whereas 4 missense variants, 3 deletions and 3 synonymous mutations were not reported in the dbSNP database but were identified in the control subjects. However, there is no significant association of these mutations with autism risk. Interestingly, there was a statistically significant association of neurexin-1 SNP P300P (rs2303298) with risk of autism (26.2% vs. 13.8%; χ(2) = 22.487; p = 3.45E-006; OR = 2.152 (1.559-2.970)). Our data suggest a possible association of neurexin-1 with autism risk in Chinese Han population, warranting further large-scale study on this gene.
authors.affiliation: School of Biological Science and Technology, Central South University, Changsha, Hunan, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Guanglei
authors.initials: G
authors.lastname: Xun
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Xu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xiong
authors.forename: Lu
authors.initials: L
authors.lastname: Xia
authors.forename: Deyuan
authors.initials: D
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001321:Autistic Disorder / Q000208:ethnology / Q000235:genetics*; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules