Human neurons carrying the syndromic autism mutation NLGN4-R704C also formed more excitatory synapses but with increased functional synaptic transmission due to a postsynaptic mechanism, while genetic loss of NLGN4 did not significantly affect synapses in the human neurons analyzed.
Here, we analysed the effect of a single amino-acid substitution (R704C) that targets a conserved arginine residue in the cytoplasmic sequence of all neuroligins, and that was associated with autism in neuroligin-4.
Several SNPs were significantly associated with altered risk of HD in the Chinese Han population, including rs1421589 within <i>NRXN1</i>, rs11795613 and rs4844285 within <i>NLGN3,</i> as well as rs5961397, rs7157669 and rs724373 within <i>NLGX4X</i> (all P<0.05).
According to both the European and the Italian control groups, a 6-marker haplotype on <i>NLGN4X</i> (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, <i>p</i>-value = 2.58 × 10<sup>-6</sup> for the European controls; odds ratio = 2.42, <i>p</i>-value = 6.33 × 10<sup>-3</sup> for the Italian controls).
According to both the European and the Italian control groups, a 6-marker haplotype on <i>NLGN4X</i> (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, <i>p</i>-value = 2.58 × 10<sup>-6</sup> for the European controls; odds ratio = 2.42, <i>p</i>-value = 6.33 × 10<sup>-3</sup> for the Italian controls).
According to both the European and the Italian control groups, a 6-marker haplotype on <i>NLGN4X</i> (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, <i>p</i>-value = 2.58 × 10<sup>-6</sup> for the European controls; odds ratio = 2.42, <i>p</i>-value = 6.33 × 10<sup>-3</sup> for the Italian controls).
According to both the European and the Italian control groups, a 6-marker haplotype on <i>NLGN4X</i> (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, <i>p</i>-value = 2.58 × 10<sup>-6</sup> for the European controls; odds ratio = 2.42, <i>p</i>-value = 6.33 × 10<sup>-3</sup> for the Italian controls).
According to both the European and the Italian control groups, a 6-marker haplotype on <i>NLGN4X</i> (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, <i>p</i>-value = 2.58 × 10<sup>-6</sup> for the European controls; odds ratio = 2.42, <i>p</i>-value = 6.33 × 10<sup>-3</sup> for the Italian controls).
According to both the European and the Italian control groups, a 6-marker haplotype on <i>NLGN4X</i> (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, <i>p</i>-value = 2.58 × 10<sup>-6</sup> for the European controls; odds ratio = 2.42, <i>p</i>-value = 6.33 × 10<sup>-3</sup> for the Italian controls).
Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of these reside in their extracellular domains except for a single point mutation in the cytoplasmic domain of NLGN4X in which an arginine is mutated to a cysteine (R704C).
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)].
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)].
In the preliminary study of specific exons of NLGN3 and NLGN4 genes, we identified the p.K378R substitution (c.1597 A > G) in exon 5 of the NLGN4 gene in a patient who was found to have mild autism and normal IQ at 3 years of age.