الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Autism spectrum disorder is a clinically and etiologically heterogeneous condition with a strong genetic component. Impairment in sensory processing have long been reported in individuals with ASD; however, findings across studies are extremely heterogeneous, frequently contradictory, and do not converge on a specific pattern of sensory features as a hallmark of ASD. Better understanding of the heterogeneity of autism could generate useful information that may aid in understanding and study of its etiology, diagnosis, treatment and prognosis. Several candidate genes are emerging as promising genes for ASD and may pave way in elucidating its biological understanding. One example is SHANK3 on terminal chromosome 22q. SHANK3 mutations have been found in approximately 2% of ASD cases and its loss results in disruption of synaptic function. Studying the copy number variations (CNVs) of one such gene, SHANK3, and the associated phenotype in patients with ASD could provide insights that will guide future ASD treatments and interventions.
This study was undertaken to assess SHANK3 CNVs in children with ASD and elucidate their sensory processing patterns using the Short Sensory Profile (SSP).
To achieve this goal, a total number of forty Egyptian children diagnosed to have ASD, according to the Diagnostic and Statistical Manual of Mental Disorders—Fifth Edition, were included in the study.
All participants were assessed using the Autism Diagnostic Interview-Revised (ADI-R). Severity of autism was assessed using Childhood Autism Rating Scale (CARS). Short Sensory Profile (SSP) was used to evaluate atypical sensory behavior. SHANK3 CNVs were measured in these children using Multiplex Ligation-dependent Probe Amplification technique.
Evaluation of SHANK3 CNV revealed that three children of the 40 participants (7.5%) had CNVs in the form of microduplication at 22q13.3 that involved SHANK3 and/or its flanking region.
On analyzing the SSP results statistically, 77.5% of cases (n= 31 out of 40) fell into the category of probable and definite differences from what is seen in typically developing children on the SSP overall score. The cases showed multimodal symptoms the greatest difference was for underresponsive/seeks sensation domain followed by tactile sensitivity, while hypo-activity (low energy/weak domain) showed the lowest difference from normal. The CARS was found to be negatively correlated with the SSP total and all subscales scores. In other words, children with more severe autism had more sensory symptoms.
To assess impact of abnormal sensory processing on autism core symptoms, correlations were carried between SSP and ADI-R three domains. The ADIR three domains were found to be negatively correlated with the SSP total and almost all subscales scores except for low energy/weak domain. In other words, children showing more sensory symptoms had poorer social reciprocity, poorer communication skills and more restrictive/ repetitive behaviors.
As regard clinical phenotype of the three duplication cases, the first positive case involved a 3-year-old boy (one of twins) with moderate nonverbal autism, a family history of seizures, mild intellectual disability (ID), and symptoms of hyperactivity. His total SSP score fell into the category of definite difference from normal. He showed definite differences from normal in the following SSP domains: tactile sensitivity, under-responsive/ seeks sensation, low-energy/weak, and auditory filtering. In addition, he showed a probable difference from normal in the taste/ smell sensitivity and visual/auditory sensitivity domains.
The second case was for a 5-year-old girl diagnosed with Asperger syndrome, ADHD, and epilepsy. Her cousin also had autism as well as learning disabilities and borderline intelligence functioning. Her total SSP score fell into the category of typical performance except for probable difference from normal in the low-energy/weak subscale.
The third case was for a 4-year-old boy with moderate-to-severe nonverbal autism, mild ID (which was also shown in his paternal aunt), and symptoms of hyperactivity. Electroencephalogram (EEG) showed subcortical epileptic activity. His total SSP score fell into the category of definite difference from normal in both total and subscale scores.