Autism spectrum disorder (ASD) is a group of developmental pathologies that impair social communication and cause repetitive behaviors. The suggested roles of noncoding RNAs in pathology led us to perform a comparative analysis of the microRNAs expressed in the serum of human ASD patients. The analysis of a cohort of 45 children with ASD revealed that six microRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) were expressed at low to very low levels compared to those in healthy controls. A similar but less pronounced decrease was registered in the clinically unaffected parents of the sick children and in their siblings but never in any genetically unrelated control. Results consistent with these observations were obtained in the blood, hypothalamus and sperm of two of the established mouse models of ASD: valproic acid-treated animals and Cc2d1a +/− heterozygotes. In both instances, the same characteristic miRNA profile was evidenced in the affected individuals and inherited together with disease symptoms in the progeny of crosses with healthy animals. The consistent association of these genetic regulatory changes with the disease provides a starting point for evaluating the changes in the activity of the target genes and, thus, the underlying mechanism(s). From the applied societal and medical perspectives, once properly confirmed in large cohorts, these observations provide tools for the very early identification of affected children and progenitors. Autism spectrum disorders (ASDs) encompass a range of disorders characterized by impaired social interactions and communications, together with repetitive stereotypic behaviors (refs. 1-5 for recent reviews). The genetic architecture underlying the range of ASD symptoms has been investigated (reviewed by Iakoucheva et al. 1). Mutations in more than 100 genes involved in brain development and neural activity have been identified in patients and are thought to confer a risk for ASD 2,3 , but a constant association that would suggest a causal relationship has not been observed. The same conclusion was recently reached from a large-scale exon sequencing analysis 4. Hence, mouse models that reproduce characteristic elements of the disease have been developed 5. As in other instances, attention has recently been focused on a peculiar class of regulatory alterations that modifies noncoding (nc) RNAs 6 with putative regulatory functions in the synthesis of proteins. One class of these alterations comprises the genes encoding 22 nt-long RNA (often abbreviated miRNAs) that regulate the expression of homologous target genes by blocking translation and inducing the degradation of the mRNAs 7. Among the miRNA genes in the mammalian genome (several hundred in the human genome), a large subset is expressed in the brain 8 , and dysfunctions of particular miRNAs have been tentatively associated with neuropathological conditions, including ASD 9,10 , with however diverging patterns of expression. They may reflect still unknown complexities of the dis...

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Classical autism belongs to a group of heterogeneous disorders known as autism spectrum disorders (ASD). Autism is defined as a neurodevelopmental disorder, characterized by repetitive stereotypic behaviors or restricted interests, social withdrawal, and communication deficits. Numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism but the etiology of this disorder is unknown in many cases. CC2D1A gene has been linked to mental retardation (MR) in a family with a large deletion before. Intellectual disability (ID) is a common feature of autistic cases. Therefore we aimed to investigate the expressions of CC2D1A and HTR1A genes with the diagnosis of autism in Turkey. Forty-four autistic patients (35 boys, 9 girls) and 27 controls were enrolled and obtained whole blood samples to isolate RNA samples from each participant. CC2D1A and HTR1A gene expressions were assessed by quantitative Real-Time PCR (qRT-PCR) in Genome and Stem Cell Center, Erciyes University. Both expressions of CC2D1A and HTR1A genes studied on ASD cases and controls were significantly different (p < 0.001). The expression of HTR1A was undetectable in the ASD samples. Comparison of ID and CC2D1A gene expression was also found statistically significant (p = 0.028). CC2D1A gene expression may be used as a candidate gene for ASD cases with ID. Further studies are needed to investigate the potential roles of these CC2D1A and HTR1A genes in their related pathways in ASD.

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