Positive association of neuroligin-4 gene with nonspecific mental retardation in the Qinba Mountains Region of China

Abstract

The results suggest a positive association between the genetic variants of the NLGN4 and NSMR in the Chinese children from Qinba Mountains Region.

Association Analysis of Noncoding Variants in Neuroligins 3 and 4X Genes with Autism Spectrum Disorder in an Italian Cohort

“…Nonetheless, our results are partially in agreement with Qi and collaborators (2009) that reported a positive association between SNPs in NLGN4X (rs6638575, rs3810686, rs1882260) and NSMR in a Chinese population [36]. In this regard, four putative haplotype combinations (rs3810686(T), rs1882260(T)), (rs3810686(C), −rs1882260(C)) and (rs6638575(G), rs3810686(T), rs18882260(T)) and (rs6638575(A), rs3810686(C), rs18882260(C)), in the sixth exon of NLGN4X have been reported as positively associated to NSMR in this Chinese cohort [36].…”

“…Deletion of exons 4, 5, and 6 in NLGN4X have been also found in autistic children, suggesting that alternative splicing variants might lead to abnormal neuroligin function in ASD [29,30]. Moreover, several noncoding genetic variants have been specifically found in ASD patients [31,32,33,34,35,36,37]. All these variations often segregate into ASD families [12,13] and can also be associated with different cognitive phenotypes, such as intellectual and language disabilities [32,37], highlighting the role of neuroligins in the ASD pathogenesis.…”

“…A three-marker haplotype (rs11795613(A), rs4844285(G), rs4844286(T)), with a significant male bias, has been suggested, supporting the hypothesis that defects of the synapse might have a role in ASD pathogenesis [6]. In addition, three haplotype sets in NLGN4X (rs3810686(T), rs1882260(C)), (rs6638575(G), rs3810686(T), rs18882260(T)) and (rs6638575(A), rs3810686(C), rs18882260(C)), have been positively associated with nonspecific mental retardation (Intelligence Quotients IQs < 70) and social disability scores ≤ 8 [36] and genetic variants in NLGN4X also have a significant effect on male cognitive abilities, highlighting the role of neuroligins in psychiatric conditions [37]. …”

“…Considering all these evidences and starting from an Italian ASD sample set, we assessed the effects of three noncoding genetic variants in NLGN3 , already reported as associated with ASD in a Chinese cohort [6], and six common single nucleotide polymorphisms (SNPs) in NLGN4X , only partially described in literature [36], with the final aim to validate the selected genetic variants as susceptibility loci for ASD.…”

Gender Differences in Cognitive Ability Associated with Genetic Variants of <i>NLGN4</i>

“…Recent studies have identified mutations in the genes encoding NLGN4 as a cause of autism spectrum disorders, Tourette's syndrome, learning disability and/ or schizophrenia [10][11][12][13][14][15] . A positive association between the genetic variants of NLGN4 and nonspecific mental retardation children of the Qinba region in China was also demonstrated in our previous study [16] . The description of the various mutations in NLGN4 seems to provide overwhelming evidence for a role of this gene in cognitive diseases.…”