Variable phenotype expression in a family segregating microdeletions of the and autism spectrum disorder susceptibility genes.

NPJ Genom Med 2017 May;2

Program in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.

Autism Spectrum Disorder (ASD) is a developmental condition of early childhood onset, which impacts socio-communicative functioning and is principally genetic in etiology. Currently, more than 50 genomic loci are deemed to be associated with susceptibility to ASD, showing and inherited unbalanced copy number variants (CNVs) and smaller insertions and deletions (indels), more complex structural variants (SVs), as well as single nucleotide variants (SNVs) deemed of pathological significance. However, the phenotypes associated with many of these genes are variable, and penetrance is largely unelaborated in clinical descriptions. This case report describes a family harboring two CNV microdeletions, which affect regions of and - each well-established in association with risk of ASD and other neurodevelopmental disorders. Although each CNV would likely be categorized as pathologically significant, both genomic alterations are transmitted in this family from an unaffected father to the proband, and shared by an unaffected sibling. This family case illustrates the importance of recognizing that phenotype can vary among exon overlapping variants of the same gene, and the need to evaluate penetrance of such variants in order to properly inform on risks.

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http://dx.doi.org/10.1038/s41525-017-0020-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482711PMC
May 2017
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