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Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2016

Open Access 01-12-2016 | Research

Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects

Authors: Carla Lintas, Roberto Sacco, Antonio M. Persico

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2016

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Abstract

Background

Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients.

Methods

In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval.

Results

ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from −458 to −223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from −222 to +1 bp. The most upstream promoter region (−458 to −364 bp) is methylated only in ASD brains, while the most downstream region (−131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls.

Conclusions

The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.
Appendix
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Metadata
Title
Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
Authors
Carla Lintas
Roberto Sacco
Antonio M. Persico
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2016
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/s11689-016-9151-z

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