What are the genetic changes related to isolated lissencephaly sequence ?
Mutations in the PAFAH1B1, DCX, or TUBA1A gene can cause ILS. PAFAH1B1 gene mutations are responsible for over half of ILS cases; DCX gene mutations cause about 10 percent of cases; and TUBA1A gene mutations cause a small percentage of ILS. These genes provide instructions for making proteins that are involved in the movement (migration) of nerve cells (neurons) to their proper locations in the developing brain. Neuronal migration is dependent on cell structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules form scaffolding within the cell that elongates in a specific direction, altering the cytoskeleton and moving the neuron. The protein produced from the TUBA1A gene is a component of microtubules. The proteins produced from the DCX and PAFAH1B1 genes promote neuronal migration by interacting with microtubules.  Mutations in any of these three genes impair the function of microtubules and the normal migration of neurons during fetal development. As a result, the layers of the cerebral cortex are disorganized and the normal folds and grooves of the brain do not form. This impairment of brain development leads to the smooth brain appearance and the resulting neurological problems characteristic of ILS.  Some individuals with ILS do not have an identified mutation in any of these three genes; the cause of the condition in these individuals may be unidentified mutations in other genes that affect neuronal migration or other unknown factors.