Genetic Disruption Points To Autism And Cerebral Palsy Link

A genetic signal common to both cerebral palsy and autism has been uncovered by researchers at the University of Adelaide.

Researchers also demonstrated common underlying molecular pathways in clinically diverse cerebral palsy. They say both findings add significantly to the weight of evidence for underlying genetic causes of cerebral palsy.

The results come from the first large-scale study of gene expression in children with cerebral palsy. It was conducted by the University’s Australian Collaborative Cerebral Palsy Research Group in the Robinson Research Institute.

“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,”

said lead researcher Dr. Clare van Eyk, Postdoctoral Research Fellow, Adelaide Medical School, University of Adelaide.

Signalling Pathway Disruption

The researchers utilzed new RNA sequencing technology to measure the gene messengers (RNA) in cells from children with cerebral palsy.

Differential expression analysis of CP cases compared to controls

Differential expression analysis of CP cases compared to controls
Credit: Clare L. van Eyk, et al. CC-BY

Cell lines from 182 individuals with cerebral palsy were studied and many showed 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 work was supported by a Cerebral Palsy Alliance Research Foundation Innovative Research Grant, Australian National Health and Medical Research Council Project Grants, Australian National Health and Medical Research Council Fellowship, Ter Meulen Fonds stipendium, and Tenix Foundation Infrastructure funding to the Australian Collaborative Cerebral Palsy Research Group.

Clare L. van Eyk, Mark A. Corbett, Alison Gardner, Bregje W. van Bon, Jessica L. Broadbent, Kelly Harper, Alastair H. MacLennan & Jozef Gecz
Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
Translational Psychiatry volume 8, Article number: 88 (2018) doi:10.1038/s41398-018-0136-4

Top Image: Network identified by ingenuity pathway analysis. Credit: Clare L. van Eyk, et al. CC-BY