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Developmental biology - Genes and Cerebral Palsy

Gene signal links cerebral palsy and autism

University of Adelaide researchers have uncovered a genetic signal common to both cerebral palsy and autism...


The finding comes from the first large-scale study of gene expression in children with cerebral palsy. Research from the University's Australian Collaborative Cerebral Palsy Research Group in the Robinson Research Institute, also shows common underlying molecular pathways in even clinically diverse cerebral palsy. Both findings add to the evidence of underlying genetic causes for cerebral palsy.
"Cerebral palsy is the most common motor disability of childhood with a frequency of around two in every 1000 live births. We know that, like autism, it's a disorder of brain development primarily during pregnancy. But the underlying causes of cerebral palsy are still poorly understood."

Clare van Eyk PhD, Postdoctoral Research Fellow, Adelaide Medical School, University of Adelaide, Australia and lead researcher.

Using new RNA sequencing technology, researchers measured RNA gene messengers from cell lines of 182 individuals with cerebral palsy showing disruption of cell signalling and inflammatory pathways, as seen in some children with autism.

"The results showed that the neurological or signalling pathways being disrupted in children with cerebral palsy overlap with those disruptions seen in autism," says Dr van Eyk. "This supports a common biological change in both cerebral palsy and autism. Autism and cerebral palsy do sometimes co-exist, which further underlines common causation in some individuals."

This is the latest in a series of studies from the University of Adelaide which have found increasing numbers of genetic mutations that are the likely cause of cerebral palsy. Using this data together with existing DNA sequencing results increases the proportion of individuals with a likely genetic cause to around 25%.

The University's Cerebral Palsy Research Group is led by Emeritus Professor Alastair MacLennan and Professor Jozef Gecz, Channel 7 Children's Research Foundation Chair for the Prevention of Childhood Disability. Their research leads the world in an increasing genetic basis to cerebral palsy.
"This research continues to refute the historical assumption that cerebral palsy is often due to difficulties at birth."

Emeritus Professor Alastair MacLennan PhD.

This study has been published in Translational Psychiatry and was supported by the Cerebral Palsy Alliance Research Foundation.

Abstract
Cerebral palsy (CP) is the most common motor disability of childhood. It is characterised by permanent, non-progressive but not unchanging problems with movement, posture and motor function, with a highly heterogeneous clinical spectrum and frequent neurodevelopmental comorbidities. The aetiology of CP is poorly understood, despite recent reports of a genetic contribution in some cases. Here we demonstrate transcriptional dysregulation of trophic signalling pathways in patient-derived cell lines from an unselected cohort of 182 CP-affected individuals using both differential expression analysis and weighted gene co-expression network analysis (WGCNA). We also show that genes differentially expressed in CP, as well as network modules significantly correlated with CP status, are enriched for genes associated with ASD. Combining transcriptome and whole exome sequencing (WES) data for this CP cohort likely resolves an additional 5% of cases separated to the 14% we have previously reported as resolved by WES. Collectively, these results support a convergent molecular abnormality in CP and ASD.

Authors: Clare L. van Eyk, Mark A. Corbett, Alison Gardner, Bregje W. van Bon, Jessica L. Broadbent, Kelly Harper, Alastair H. MacLennan & Jozef Gecz


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May 16, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




Emeritus Professor Alastair MacLennan (University of Adelaide) with Matthew Reinertsen, who has cerebral palsy. Researchers have discovered that many cases of cerebral palsy may have genetic causes. Image credit: Robinson Research Institute, University of Adelaide.


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