PUBLICATION
Targeted resequencing identifies genes with recurrent variation in cerebral palsy
- Authors
- van Eyk, C.L., Corbett, M.A., Frank, M.S.B., Webber, D.L., Newman, M., Berry, J.G., Harper, K., Haines, B.P., McMichael, G., Woenig, J.A., MacLennan, A.H., Gecz, J.
- ID
- ZDB-PUB-191110-4
- Date
- 2019
- Source
- NPJ genomic medicine 4: 27 (Journal)
- Registered Authors
- Newman, Morgan
- Keywords
- Genetic testing, Molecular medicine, Neurodevelopmental disorders, Paediatric neurological disorders
- MeSH Terms
- none
- PubMed
- 31700678 Full text @ NPJ Genom Med
Citation
van Eyk, C.L., Corbett, M.A., Frank, M.S.B., Webber, D.L., Newman, M., Berry, J.G., Harper, K., Haines, B.P., McMichael, G., Woenig, J.A., MacLennan, A.H., Gecz, J. (2019) Targeted resequencing identifies genes with recurrent variation in cerebral palsy. NPJ genomic medicine. 4:27.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping