الفهرس 
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Abstract
Autism Spectrum Disorder (ASD) is defined by the Diagnostic Statistical Manual of Mental Disorders 5 (DSM-5) as a neurobehavioral disorder manifested by persistent deficits in social interaction, deficits in developing, understanding and maintaining relationships, as well as abnormal and fixed interests and repetitive behavior.
The worldwide estimated prevalence of individuals with ASD Diagnosis is strikingly high with prevalence varying across numerous studies, but it is estimated that one in 160 children has an ASD worldwide, and it is expected to increase globally.
The etiology of ASD is not well characterized, current research suggests that ASD is likely explained by a multifactorial etiology that includes genetic and environmental risk factors, which interact in a cumulative way to reach a threshold for onset. Genetics is a well-established risk factor in the etiology of ASD.
Disturbances in both folate and methylation metabolism can lead to abnormalities in chromosomal integrity. Among these genetic alterations, methionine, an essential amino acid and precursor of S-adenosylmethionine, is a universal methyl-group donor involved in methylation reactions including DNA methylation which is critical for regulating gene expression and gene integrity.
This reaction is regulated by one important enzyme, methionine synthase (MTR). Using cobalamin as a cofactor, methionine synthase (MTR) converts homocysteine into methionine and transfers methyl groups from 5-methyltetrahydrofolateto homocysteine, producing tetrahydrofolate for nucleic acid synthesis and methionine for methylation reactions.
The MTR gene is located at chromosome 1. The polymorphism rs1805087 (A2756G) in the MTR gene influences the activity of its encoding enzyme, leading to elevated circulating homo¬cysteine.
This study was conducted on 50 children diagnosed as having ASD according to DSM-5 criteria (American Psychiatric Association, 2013). The severity of ASD symptoms was assessed using Childhood Autism Rating Scale (CARS).
All children were recruited from the Pediatric Department- Psychiatry Clinic. Patients enrolled in this study aged from 3 – 12 years with a mean value of 6.1 ± 2.6 years. Children with concurrent neurological disorders, chronic organic diseases as blindness or deafness, history of significant head trauma or history of perinatal asphyxia were excluded from the study.
There was no significant difference between cases and controls was found regarding age, sex, order of birth, mode of delivery, NICU admission, type of feeding, Consanguinity and family history.
There was a significant difference between cases and controls as regard genotypes as GG was present among 38% of cases compared to 18% of controls. Similarly, AG was present in 50% of cases compared to 30% of controls while AA was significantly lower in cases compared to controls (12% vs 52%) more over GG genotype was shown to be associated with increased risk of autism in our population relatively to other genotypes.(P=0.026,OR 2.79, 95% CI 1.113-7.07).
The A and G allele frequencies of MTR 2756 gene polymorphism were 37%, 63% in the patient group and 67%, 33% in the control group, respectively, which was statistically highly significant (P=0.0001). Moreover G allele was shown to be associated with the increased risk of autism by 3.4 fold (OR=3.457 with 95% CI =1.93-6.185).