MTHFR Functional Polymorphism C677T and Genomic Instability in the Etiology of Idiopathic Autism in Simplex Families.

摘要

Autism Spectrum Disorder (ASD) are a group of neurodevelopmental disorders that are caused by a range of factors, including: genetic, epigenetic and environmental, with a genetic/epigenetic model proposed (Jiang et al., 2004). While a main focus of autism research remains on the genetic causes, more and more attention was srawn to the role epigenetic factors play, as it has been shown to play a role in idiopathic autism. With our previous published study revealed significantly association of C677T polymorphism in MTHFR gene with idiopathic autism in Simplex (SPX) autism families ( Liu et al., 2011); and the proven facts that de novo CNVs rates are consistently high in SPX ASD (5.8%-10.2%) versus familial ASD (2-3%), we hypothesize that low-activity MTHFR 677T allele leads to increase global DNA hypomethylation and consequently results in increased generation of de novo CNVs bringing about a higher risk for developing sporadic cases of autism. We propose to test 1) the association of MTHFR 677T allele with rate of ASD related de novo CNVs; 2) the association of MTHFR 677T allele with increased level of global hypomethylation; and 3) the association of level of global hypomethylation with increased rate of ASD related de novo CNVs.