الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Autism is a relatively common neurodevelopmental disorder. The CDC stated that its prevalence is 1 in 54 children aged 8 years old, with a male to female ratio of 4 to 1. It is clinically diagnosed based on DSM-5 diagnostic criteria. Autism spectrum disorders (ASD) are recognized as a single disorder encompassing infantile autism, Asperger‘s disease, and pervasive neurodevelopmental disorders not otherwise specified (PDD-NOS). The most commonly used tool for the assessment of ASD severity is the Childhood Autism Rating Scale (CARS), where severity is divided based on the total score into mild, moderate and severe.
Several co-morbidities accompany ASD such as gastrointestinal, psychiatric and neurological disorders including attention deficit hyperactivity disorder, anxiety, obsessive compulsive disorder and epilepsy. Contrary to syndromic autism that usually has definite causative genes and established paths and is associated with other neurological or somatic manifestations, the majority of ASD cases are non-syndromic or idiopathic with unknown molecular and biological pathways.
More than a thousand autism risk genes have been identified, where most of the genetic mutations are de-novo with emphasis on the role genetic-environmental interactions in ASD pathogenesis. Epigenetic changes alter gene expression without affecting the underling DNA sequence. They participate in the pathogenesis of several neurodevelopmental disorders including ASD. Non-coding RNAs, particularly micro RNAs, comprise single stranded short sequences of non coding RNAs that induce post transcriptional repression of mRNA.
The aim of this work was to measure the relative expression levels of a panel of circulating microRNAs (miR-146a-5p, miR-106b-5p and miR-148a-5p) in a group of Egyptian autistic children to determine the diagnostic performance of the studied panel as a
Summary, Conclusion and Recommendations
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potential non invasive molecular marker for ASD. Functional enrichment analysis and target gene prediction of the studied s was also performed.
Peripheral blood samples were collected from 16 children with ASD and 34 age and gender matched healthy controls. Childhood autism rating scale (CARS) was used as a scoring system for assessing the severity of ASD. Relative expression levels of plasma miR-106b-6p, -146a-5p and -148b-5p were determined using TaqMan real time polymerase chain reaction.
The present work demonstrated significant upregulations in the plasma levels of the three studied microRNAs in autistic children compared to the healthy ones. The ROC curve generated cut off values for each of the studied microRNAs showed that miR-148a-5p achieved the highest sensitivity (93.75%) and specificity (100%), whereas miR-106b-5p and -146a-5p gave the same sensitivity (87.5%), but variable specificity (97.14% for the former and 91.43% for the latter).
Several bioinformatics softwares were used in the present work. Functional enrichment analysis by the bioinformatics software miRPathDB 2.0 showed that 146a-5p targeted the leucocyte transendothelial migration pathway. Moreover, miR-146a and -106b were enriched in the tumor necrosis factor signaling pathway.
As regards the target gene prediction done by mienturnet software, it computed SIKE1 as a common gene for the three studied microRNAs. SIKE1 acts as a suppressor of toll like receptor-3 which in turn disturbs neurite outgrowth, synapsis formation and neural connectivity.