Misra, S;
Peters, G;
Barnes, E;
Ardern-Holmes, S;
Webster, R;
Troedson, C;
Mohammad, SS;
... Dale, RC; + view all
(2019)
Yield of comparative genomic hybridization microarray in pediatric neurology practice.
Neurology Genetics
, 5
(6)
, Article e367. 10.1212/NXG.0000000000000367.
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Abstract
OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30–10.51]), cortical visual impairment (OR 2.73 [1.18–6.28]), dysmorphism (OR 2.75 [1.38–5.50]), and microcephaly (OR 2.16 [1.01–4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02–8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01–1.38]). CONCLUSIONS: the use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly.
| Type: | Article |
|---|---|
| Title: | Yield of comparative genomic hybridization microarray in pediatric neurology practice |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/NXG.0000000000000367 |
| Publisher version: | https://doi.org/10.1212/NXG.0000000000000367 |
| Language: | English |
| Additional information: | © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | All Genetics, All Epilepsy/Seizures, All Pediatric, All Clinical Neurology, Developmental disorders, Antiepileptic drugs, Ion channel gene defects ,Neonatal seizures, Infantile spasms |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10088802 |
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