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

Since involved in synaptic transmission and located on X-chromosome, neuroligins 3 and 4X have been studied as good positional and functional candidate genes for autism spectrum disorder pathogenesis, although contradictory results have been reported. Here, we performed a case-control study to assess the association between noncoding genetic variants in NLGN3 and NLGN4X genes and autism, in an Italian cohort of 202 autistic children analyzed by high-resolution melting. The results were first compared with data from 379 European healthy controls (1000 Genomes Project) and then with those from 1061 Italian controls genotyped by Illumina single nucleotide polymorphism (SNP) array 1M-duo. Statistical evaluations were performed using Plink v1.07, with the Omnibus multiple loci approach. According to both the European and the Italian control groups, a 6-marker haplotype on NLGN4X (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, p-value = 2.58 × 10-6 for the European controls; odds ratio = 2.42, p-value = 6.33 × 10-3 for the Italian controls). Furthermore, several haplotype blocks at 5-, 4-, 3-, and 2-, including the first 5, 4, 3, and 2 SNPs, respectively, showed a similar association with autism. We provide evidence that noncoding polymorphisms on NLGN4X may be associated to autism, suggesting the key role of NLGN4X in autism pathophysiology and in its male prevalence.

Study on the Association among Mycotoxins and other Variables in Children with Autism.

Environmental factors and genetic susceptibility are implicated in the increased risk of autism spectrum disorder (ASD). Mycotoxins are agricultural contaminants of fungal origin that represent real risk factors for human health and especially for children. Thus, the main hypothesis of this work is that the deterioration of the clinical manifestation of autism in children may result from the exposure to mycotoxins through the consumption of contaminated food. Within a cross-sectional study, a group of autistic children (n = 172) and a group of controls (n = 61) (siblings and non-parental) were recruited in North and South Italy. All children had blood and urine samples taken, for testing some mycotoxins by a LC-MS/MS validated method. Blood samples were also tested for assessing specific IgG against food and fungal antigens and cytokines. The analyses outputs highlighted statistically significant differences comparing mycotoxins levels between (i) children groups both in urine (deoxynivalenol and de-epoxydeoxynivalenol, p = 0.0141 and p = 0.0259, respectively) and serum (aflatoxin M1, ochratoxin A and fumonisin B1, p = 0.0072, p = 0.0141 and p = 0.0061, respectively); (ii) a group of selected fungal IgGs, and IgGs against wheat and gluten and (iii) cytokines. These results suggest the need for a deeper examination of the role that mycotoxins may have on the etiology of ASD.

Functional classifications for cerebral palsy: correlations between the gross motor function classification system (GMFCS), the manual ability classification system (MACS) and the communication function classification system (CFCS).

This study aimed to investigate a possible correlation between the gross motor function classification system-expanded and revised (GMFCS-E&R), the manual abilities classification system (MACS) and the communication function classification system (CFCS) functional levels in children with cerebral palsy (CP) by CP subtype. It was also geared to verify whether there is a correlation between these classification systems and intellectual functioning (IF) and parental socio-economic status (SES). A total of 87 children (47 males and 40 females, age range 4-18 years, mean age 8.9±4.2) were included in the study. A strong correlation was found between the three classifications: Level V of the GMFCS-E&R corresponds to Level V of the MACS (rs=0.67, p=0.001); the same relationship was found for the CFCS and the MACS (rs=0.73, p<0.001) and for the GMFCS-E&R and the CFCS (rs=0.61, p=0.001). The correlations between the IQ and the global functional disability profile were strong or moderate (GMFCS and IQ: rs=0.66, p=0.001; MACS and IQ: rs=0.58, p=0.001; CFCS and MACS: rs=0.65, p=0.001). The Kruskal-Wallis test was used to determine if there were differences between the GMFCS-E&R, the CFCS and the MACS by CP type. CP types showed different scores for the IQ level (Chi-square=8.59, df=2, p=0.014), the GMFCS-E&R (Chi-square=36.46, df=2, p<0.001), the CFCS (Chi-square=12.87, df=2, p=0.002), and the MACS Level (Chi-square=13.96, df=2, p<0.001) but no significant differences emerged for the SES (Chi-square=1.19, df=2, p=0.554). This study shows how the three functional classifications (GMFCS-E&R, CFCS and MACS) complement each other to provide a better description of the functional profile of CP. The systematic evaluation of the IQ can provide useful information about a possible future outcome for every functional level. The SES does not appear to affect functional profiles.