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Open Access 01-12-2014 | Research

CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems

Authors: Sébastien Chénier, Grace Yoon, Bob Argiropoulos, Julie Lauzon, Rachel Laframboise, Joo Wook Ahn, Caroline Mackie Ogilvie, Anath C Lionel, Christian R Marshall, Andrea K Vaags, Bita Hashemi, Karine Boisvert, Géraldine Mathonnet, Frédérique Tihy, Joyce So, Stephen W Scherer, Emmanuelle Lemyre, Dimitri J Stavropoulos

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2014

Abstract

Background

The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking.

Methods

We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder.

Results

Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene.

Conclusions

The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals.

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Title: CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems
Authors: Sébastien Chénier
Grace Yoon
Bob Argiropoulos
Julie Lauzon
Rachel Laframboise
Joo Wook Ahn
Caroline Mackie Ogilvie
Anath C Lionel
Christian R Marshall
Andrea K Vaags
Bita Hashemi
Karine Boisvert
Géraldine Mathonnet
Frédérique Tihy
Joyce So
Stephen W Scherer
Emmanuelle Lemyre
Dimitri J Stavropoulos
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Neurodevelopmental Disorders / Issue 1/2014
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI: https://doi.org/10.1186/1866-1955-6-9

At a glance: The STEP trials

Springer Medicine

CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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