CASK Gene Plays Role in Microcephaly

A new study published in the July print of Experimental Neurology reports that haploinsufficiency of the CASK gene induces post-transcriptional and metabolic changes that could cause microcephaly. The team from Virginia Tech reports findings that challenge the idea that seizures could be the cause of smaller brains. 

"We developed and studied a 'face-valid' genetic animal model and determined that global electrical activity in the brain is not affected," says Paras Patel, co-author of the study.  "We confirmed that epilepsy is indeed of very low frequency, suggesting that it is not underlying the cellular death and abnormality in brain volume."

In order to understand the functional role of CASK genes, they studied a mouse model where half of the cells did not have the gene—this proportion is genetically similar to the majority of human cases. The team found that the mice had abnormalities that would negatively impact the communication between brain cells, as well as molecular changes that affect cell protein activity. 

“Strikingly, significant numbers of molecular changes that we observed occur in proteins related to cellular energy production and other aspects of mitochondrial function," says corresponding author Konark Mukherjee.  "The role for CASK at the mitochondria provides interesting future directions into how this function could explain diminished brain size and dysregulated function in cases of CASK mutation in humans," they conclude.