Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism

Transl Psychiatry. 2018 Apr 23;8(1):88. doi: 10.1038/s41398-018-0136-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / metabolism*
  • Cell Line
  • Cerebral Palsy / genetics*
  • Cerebral Palsy / metabolism*
  • Cohort Studies
  • Exome Sequencing
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Glycoproteins
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, trkB
  • Signal Transduction*
  • Transcriptome*

Substances

  • Membrane Glycoproteins
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, trkB
  • tropomyosin-related kinase-B, human