Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Sci Rep. 2017 Oct 3;7(1):12575. doi: 10.1038/s41598-017-12981-5.


Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / metabolism
  • Autism Spectrum Disorder / physiopathology
  • Axons / metabolism
  • Cell Differentiation / genetics
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism*
  • Dystrophin / genetics*
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / physiopathology
  • Mutation
  • Neurons / metabolism
  • Neuropsychological Tests
  • Phenotype
  • Protein Isoforms / genetics*
  • Purkinje Cells / metabolism
  • Purkinje Cells / pathology
  • Transcriptome / genetics


  • Dystrophin
  • Protein Isoforms