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Updated: Oct 25, 2025

In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
How does genetic variation modify ND-CNV phenotypes?
Thomas J Dinneen1, Fiana Ní Ghrálaigh2, Ruth Walsh1
1Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Abstract:
Rare copy-number variants (CNVs) associated with neurodevelopmental disorders (NDDs), i.e., ND-CNVs, provide an insight into the neurobiology of NDDs and, potentially, a link between biology and clinical outcomes. However, ND-CNVs are characterised by incomplete penetrance resulting in heterogeneous carrier phenotypes, ranging from non-affected to multimorbid psychiatric, neurological, and physical phenotypes. Recent evidence indicates that other variants in the genome, or 'other hits', may partially explain the variable expressivity of ND-CNVs. These may be other rare variants or the aggregated effects of common variants that modify NDD risk. Here we discuss the recent findings, current questions, and future challenges relating to other hits research in the context of ND-CNVs and their potential for improved clinical diagnostics and therapeutics for ND-CNV carriers.
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