No correlation between X chromosome inactivation pattern and autistic spectrum disorders in an Italian cohort of patients

Natalia Cannelli,Fiorella Gurrieri,Claudia Rendeli,Giovanni Neri,Elisabetta Tabolacci

doi:10.4236/ojgen.2011.13007

Abstract

Autistic spectrum disorders (ASD) occur more frequently in males, suggesting a major pathogenic role for genes located on the X-chromosome. The analysis of X chromosome inactivation (XCI) pattern may help to identify XCI skewing in those families in which such genes are involved, even without identifying the specific genetic mutation. In order to identify such families, we determined the XCI pattern in 40 females with ASD and 58 mothers of children with ASD, as well as in 80 matched control females. The X inactivation assay was carried out on genomic DNA extracted from peripheral blood. XCI was calculated for informative heterozygous individuals as the ratio of the peak area of two alleles of the highly polymorphic CAG repeat of the androgen receptor (AR) gene (Xq11-12). Our results indicate that there is no difference in XCI pattern both in ASD females and in the mothers of ASD patients when compared with the appropriate controls. These findings suggest that the contribution of X-linked genes to the etiology of ASD is still likely but it is not supported by X-inactivation patterns on peripheral blood cells.

Highlights

Autistic spectrum disorders (ASD) are a group of childhood neurodevelopmental disorders characterized by difficulties in socialization and communication and stereotypic behaviors
Our results indicate that there is no difference in X chromosome inactivation (XCI) pattern both in ASD females and in the mothers of ASD patients when compared with the appropriate controls
These findings suggest that the contribution of X-linked genes to the etiology of ASD is still likely but it is not supported by X-inactivation patterns on peripheral blood cells

Summary

Introduction

Autistic spectrum disorders (ASD) are a group of childhood neurodevelopmental disorders characterized by difficulties in socialization and communication and stereotypic behaviors. The prevalence of ASD is about 0.6:100, with an overall excess of males with autism in a proportion of about 4:1 in general and of 9:1 in the cases of Asperger syndrome [4], suggesting a major involvement of genes on the X chromosome. Mutations in two X-linked genes encoding neuroligins, NLGN3 and NLGN4 respectively, have been identified in males with ASD, including Asperger syndrome [5]. X chromosome inactivation (XCI) occurs early in embryonic development of somatic cells in human females to achieve gene dosage compensation with males [8]. An extremely skewed XCI can be observed in heterozygous females carrying gene mutations involved in X-linked conditions, such as X-linked intellectual disability, Barth syndrome and X-linked sideroblastic anemia [12,13,14]

Methods

Results

Conclusion