Study of genotype-phenotype correlation of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in a sample of Egyptian autistic children

Background: Classical autism belongs to a group of heterogeneous neurobehavioral disorders known as autism spectrum disorders (ASDs) characterized by abnormalities in social interaction,impaired communication,and repetitive stereotypic behaviors. Overall,there is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. This study aimed at identification of the C677T polymorphic genotypes of MTHFR gene among the Egyptian children with autism and to correlate them with different phenotypes. Subjects and methods: This case-control study included 20. children with autism (4.57 ± 1.36. years) (13. males and 7. females) and a normal control group. Assessments by DSM-IV-TR criteria,Stanford-Binet intelligence scale and childhood autism rating scale (CARS) were done. Assay for MTHFR gene mutation C677T was performed on amplified DNA by PCR and subsequent reverse hybridization to immobilized allele-specific biotinylated oligonucleotides probes. Results: The relation between low birth weight and occurrence of autism is 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); 50% of autistic patients were heterozygous (CT) for the MTHFR gene,and 15% were homozygotes for the mutant genotype (TT). For the homozygous wild type genotype,35% of patients were CC (P 0.05). The segregation of T allele in the homozygous 677TT genotype occurred in 30% of autistic children. Frequency of the T-allele in autistic children is 0.4 compared to an allele frequency of 0.3 among controls (P 0.01). According to the CARS classification,70% were severely affected of whom 42.8% were carrying the CT genotype. There was no significant difference between CARS (degree of severity of autism) and C677T polymorphism. There was no significant difference between various genotypes as regards the mean for CARS. There was no statistically significant difference as regards mean gestational age,birth weight and mean age at sitting down among the patient group with different genotypes (P . 0.05). Conclusion: Although the 677CT variant alleles significantly increased in patients with autism,it is unlikely that this association alone is sufficient to produce the complex array of symptoms associated with autism. Therefore,a search for additional genomic,metabolic,epigenetic and environmental risk factors should be undertaken. © 2014.