Study Of The C677T and 1298AC Polymorphic Genotypes Of MTHFR Gene And Phenotype Genotype Correlation In Autism Spectrum Disorder

Background:  Autism is currently known as "a behaviorally defined syndrome” manifested as impairment in social communication, repetitive routines and restricted interests .Overall, there is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. Aim of the study: This study aimed at identification of the C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample of Egyptian children with autism and to make a phenotype-genotype correlation for the autistic patients. Subjects and methods: This case-control study included 31 children with autism and 39 children in a normal control group , the  mean  age of patients and control  was comparable ( 4.5 years± 2) with more males predominance in both groups. Assessments by DSM-V-TR criteria, Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) were done. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was performed on amplified DNA by PCR with subsequent reverse hybridization and restriction fragment length polymorphisms analysis.  Results The relation between low birth weight and occurrence of autism was highly significant (P < 0.01). The delayed motor and social milestones showed a statistically highly significant difference in cases of autism compared to controls (P < 0.01). Heterozygosity for A1298C polymorphism was highest among patients (41.9%) followed by 35.5% mutant genotype CC  and 22.6% normal AA(wild ) type and  .Allele Cwas detected in patients more than in control (56.45% vs. 11.54%)(P <0.001). For C667T polymorphism, heterozygosity was also highest among patients (48,4% ) followed by wild type genotypes C677 (38.7%) and 12,9%  for mutant genotypes 667T. Allele T appeared more in patients than control (31.10 %vs. 5.13%) (P < 0.00). Heterozygosity for CT and A-C genotypes were detected equally (46.2%) among patients with severe autism (according to CARS). Conclusion There is a significant association between severity and occurrence of autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed on larger scale to explore other genes polymorphisms that may be associated with autism to correlate the genetic basis of autism.