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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2016

Open Access 01-12-2016 | Research article

Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy

Authors: Andrew E. Fry, Elliott Rees, Rose Thompson, Kiran Mantripragada, Penny Blake, Glyn Jones, Sian Morgan, Sian Jose, Hood Mugalaasi, Hayley Archer, Emma McCann, Angus Clarke, Clare Taylor, Sally Davies, Frances Gibbon, Johann Te Water Naude, Louise Hartley, Gareth Thomas, Catharine White, Jaya Natarajan, Rhys H. Thomas, Cheney Drew, Seo-Kyung Chung, Mark I. Rees, Peter Holmans, Michael J. Owen, George Kirov, Daniela T. Pilz, Michael P. Kerr

Published in: BMC Medical Genetics | Issue 1/2016

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Abstract

Background

Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy.

Methods

We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation.

Results

8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort.

Conclusions

We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults.
Appendix
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Metadata
Title
Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy
Authors
Andrew E. Fry
Elliott Rees
Rose Thompson
Kiran Mantripragada
Penny Blake
Glyn Jones
Sian Morgan
Sian Jose
Hood Mugalaasi
Hayley Archer
Emma McCann
Angus Clarke
Clare Taylor
Sally Davies
Frances Gibbon
Johann Te Water Naude
Louise Hartley
Gareth Thomas
Catharine White
Jaya Natarajan
Rhys H. Thomas
Cheney Drew
Seo-Kyung Chung
Mark I. Rees
Peter Holmans
Michael J. Owen
George Kirov
Daniela T. Pilz
Michael P. Kerr
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2016
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-016-0294-2

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