Abstract

Neurodevelopment: Copy number variants underlie cases of cerebral palsy

At least 23% of cerebral palsy has a genetic basis, due to either point mutations or large chromosomal abnormalities. Using sequence data from 186 unrelated patients, a team led by Mark Corbett from the University of Adelaide, Australia, searched the protein-coding portion of the genome for disease-causing duplications or deletions, types of mutations collectively known as copy number variants, or CNVs. The researchers singled out 7 pathogenic CNVs that they corroborated through microarray profiling and gene expression analyses. Using a zebrafish model, the researchers identified a new gene “PDCD6IP” associated with cerebral palsy and epilepsy. They also flagged another 14 CNVs that were likely pathogenic but could not be confirmed. The work highlights the need for comprehensive genetic testing to be considered early in the diagnosis of cerebral palsy.

Details

Title
Pathogenic copy number variants that affect gene expression contribute to genomic burden in cerebral palsy
Author
Corbett, Mark A 1   VIAFID ORCID Logo  ; van Eyk, Clare L 1   VIAFID ORCID Logo  ; Webber, Dani L 1 ; Bent, Stephen J 2 ; Newman, Morgan 3 ; Harper, Kelly 1 ; Berry, Jesia G 1 ; Azmanov, Dimitar N 4 ; Woodward, Karen J 5 ; Gardner, Alison E 1 ; Slee, Jennie 6 ; Pérez-Jurado, Luís A 7   VIAFID ORCID Logo  ; MacLennan, Alastair H 1 ; Gecz, Jozef 8 

1  Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia 
2  Data61, Commonwealth Scientific and Industrial Research Organisation, Ecosciences Precinct, Dutton Park, Brisbane, QLD, Australia 
3  School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia 
4  Department of Diagnostic Genomics, Queen Elizabeth II Medical Centre, PathWest, Nedlands, WA, Australia 
5  Department of Diagnostic Genomics, Queen Elizabeth II Medical Centre, PathWest, Nedlands, WA, Australia; School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia 
6  Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, WA, Australia 
7  Genetics Unit, Universitat Pompeu Fabra, Barcelona, Spain; Hospital del Mar Research Institute (IMIM) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain; SA Clinical Genetics, Women’s and Children’s Hospital & University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia 
8  Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia 
Pages
1-9
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20567944
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41525-018-0073-4
ProQuest document ID
2156486638
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.