Whole genome sequencing for copy number variant detection to improve diagnosis and management of rare diseases.
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Authors
Bowman, Pamela
Grimes, Hannah
Dallosso, Anthony R
Berry, Ian
Mullin, Stephen
Rankin, Julia
Low, Karen J
Issue Date
2024-06-05
Type
Case Reports
Journal Article
Journal Article
Language
en
Keywords
Wessex Classification Subject Headings::Paediatrics
Alternative Title
Abstract
First-line genetic investigations for rare neurological and developmental conditions have limitations in their ability to detect and characterize copy number variants (CNVs). Whole genome sequencing (WGS) offers potential advantages over other methods of CNV analysis. We aimed to demonstrate the utility of CNV detection using WGS through description of three clinical cases. WGS analysis was undertaken in three patients presenting to a national rare disease service, in whom a genetic aetiology remained uncertain after gene panel testing or microarray based comparative genomic hybridization (array CGH). In all three cases, WGS identified CNVs and confirmed zygosity and pathogenicity, resulting in genetic diagnoses of PRKN-related Parkinson disease, TAOK1-related neurodevelopmental disorder, and AP1G1-related Usmani-Riazuddin syndrome. This case series demonstrates the value of WGS analysis in identifying or better characterizing CNVs that were missed or deemed of uncertain significance using conventional methods of testing. Importantly, our approach facilitated accurate genetic diagnosis and counselling for the families involved.
Description
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press
Citation
Bowman, P.; Grimes, H.; Dallosso, AR.; Berry, I.; Mullin, S.; Rankin, J. and Low, KJ. (2024) 'Whole genome sequencing for copy number variant detection to improve diagnosis and management of rare diseases', Developmental Medicine and Child Neurology, Available at: https://doi.org/10.1111/dmcn.15985
Publisher
Wiley
License
© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.
Journal
Developmental medicine and child neurology
Volume
Issue
PubMed ID
ISSN
1469-8749