Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/122602
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Type: Journal article
Title: Targeted resequencing identifies genes with recurrent variation in cerebral palsy
Author: van Eyk, C.
Corbett, M.
Frank, M.
Webber, D.
Newman, M.
Berry, J.
Harper, K.
Haines, B.
McMichael, G.
Woenig, J.
MacLennan, A.
Gecz, J.
Citation: npj Genomic Medicine, 2019; 4(1):27-1-27-11
Publisher: Springer Nature
Issue Date: 2019
ISSN: 2056-7944
2056-7944
Statement of
Responsibility: 
C. L. van Eyk, M. A. Corbett, M. S. B. Frank, D. L. Webber, M. Newman, J. G. Berry, K. Harper, B. P. Haines, G. McMichael, J. A. Woenig, A. H. MacLennan, and J. Gecz
Abstract: A growing body of evidence points to a considerable and heterogeneous genetic aetiology of cerebral palsy (CP). To identify recurrently variant CP genes, we designed a custom gene panel of 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 cases not previously examined using next-generation sequencing technologies. Overall, 5.2% of the naïve cases (14/271) harboured a genetic variant of clinical significance in a known disease gene, with a further 4.8% of individuals (13/271) having a variant in a candidate gene classified as intolerant to variation. In the aggregate cohort of individuals from this study and our previous genomic investigations, six recurrently hit genes contributed at least 4% of disease burden to CP: COL4A1, TUBA1A, AGAP1, L1CAM, MAOB and KIF1A. Significance of Rare VAriants (SORVA) burden analysis identified four genes with a genome-wide significant burden of variants, AGAP1, ERLIN1, ZDHHC9 and PROC, of which we functionally assessed AGAP1 using a zebrafish model. Our investigations reinforce that CP is a heterogeneous neurodevelopmental disorder with known as well as novel genetic determinants.
Keywords: Genetic testing; Molecular medicine; Neurodevelopmental disorders; Paediatric neurological disorders
Rights: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 1000004367
DOI: 10.1038/s41525-019-0101-z
Grant ID: http://purl.org/au-research/grants/nhmrc/1019928
http://purl.org/au-research/grants/nhmrc/1099163
http://purl.org/au-research/grants/nhmrc/1041920
http://purl.org/au-research/grants/nhmrc/1155224
Appears in Collections:Medicine publications

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