As neuronal function is supported by astrocytes, which express dystrophin, we hypothesized that loss of dystrophin from DMD astrocytes might contribute to these cognitive defects.
We have previously shown that inadequate dystrophin in cortical neurons in mdx mice is associated with age-dependent dyshomeostasis of resting intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) and Na<sup>+</sup> ([Na<sup>+</sup>]<sub>i</sub>), elevated reactive oxygen species (ROS) production, increase in neuronal damage and cognitive deficit.
The 47 enrolled patients, defined with a Full Scale Intelligence Quotient (FSIQ) of 80.38 (one SD below average), and presenting a large and significant difference in FSIQ in relation to the site of mutation along the dystrophin gene (distal mutations associated with a more severe cognitive deficit), were showing Internalizing Problems (23.4%) and Autism Spectrum Disorders (14.8%).
The Dystrophin (Dp) gene is responsible for Duchenne muscular dystrophy (DMD), which is characterized by progressive muscular degeneration and variable degrees of cognitive impairment.
Although there is no strict genotype-phenotype correlation, particularly mutations in the distal part of the dystrophin gene are frequently associated with short stature and a high rate of microcephaly as well as cognitive impairment.
The risk of ADHD appears to be higher in patients carrying mutations predicted to affect dystrophin isoforms expressed in the brain and are known to be associated with higher risk of cognitive impairment.