Substantial elevation of telomeric oxidized bases in childhood autism

Abstract

Background

The underlying molecular mechanisms responsible for the etiology of autism and its sex-biased prevalence remain largely elusive. We have previously shown that children with non-syndromic low-functioning idiopathic autism exhibit a sexually dimorphic pattern of relative telomere length (RTL), with autistic male children having significantly shorter RTL than autistic female children, healthy controls, and paired siblings. By contrast, a number of autistic girls had longer RTLs than healthy controls. Here, we investigated levels of telomeric oxidized base (TelOB) lesions among the same study subjects and groups.

Methods

Employing a quantitative PCR (qPCR)-based method, which combines DNA digestion targeting oxidized bases and telomere measurement, TelOB lesions were measured using genomic DNA extracted from saliva samples collected from 24 children (14 male and 10 female) with autism, 10 paired siblings, and 24 sex, age, and location-matched typically-developing controls.

Results

Our findings show that both male and female autistic children exhibit substantially higher TelOB lesions at their telomeres than healthy controls and paired siblings. Interestingly, these elevated levels of TelOBs show a direct correlation with RTL values in autistic children but not in healthy controls. However, TelOB levels do not show any association with age either in the autistic children or the healthy control group.

Conclusions

Our findings open a fresh angle into autism spectrum disorders (ASD), raise new questions, and lay the foundation for further research into telomere biology and underlying molecular mechanisms involved in ASD. TelOB levels are likely set during early development and may serve as biomarkers for childhood autism.