DCX

The DCX gene provides instructions for producing a protein called doublecortin. This protein is involved in the migration of nerve cells (neurons) to their proper location in the developing brain. Doublecortin plays a role in neuronal migration by attaching (binding) to microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). In neuronal migration, microtubules help propel the neurons by forming a meshwork around the nucleus of the cell and, with the aid of other proteins, expanding and contracting the cytoskeleton to move the nucleus and whole neuron forward. Doublecortin is involved in the organization of the microtubule structures. Proper microtubule function is necessary for correct neuronal organization in the exterior of the brain (cerebral cortex).

X-linked lissencephaly - caused by mutations in the DCX gene

There are more than 60 mutations in the DCX gene that cause X-linked lissencephaly. These mutations usually result in a doublecortin protein with little or no function. The absence of functional doublecortin causes failure of the neurons to migrate to their proper location, impairing formation of the normal folds and grooves of the multi-layered cerebral cortex. This abnormality of brain development leads to the characteristic smooth brain appearance of X-linked lissencephaly.

other disorders - caused by mutations in the DCX gene

Subcortical band heterotopia is a condition of abnormal brain development. It is most often a mild form of X-linked lissencephaly. Subcortical band heterotopia occurs when neurons migrate to an area of the brain where they are not supposed to be (heterotopia), and form abnormal areas that appear as band-like clusters of white tissue underneath the gray tissue of the cerebral cortex. Since these bands are located beneath the cerebral cortex, they are said to be subcortical. The symptoms people with subcortical band heterotopia experience can vary from severe intellectual disability and epilepsy to normal intelligence with mild or no epilepsy.

Subcortical band heterotopia is usually seen in females with a mutation in one copy of the DCX gene, while males with one DCX mutation usually have X-linked lissencephaly. In a few instances the reverse has been noted, in which females developed X-linked lissencephaly and males developed subcortical band heterotopia; however, this is rare.